She didn’t read my cards. She told me to read a book: The Vagus Nerve Reset, by Anna Ferguson. I hung up mildly annoyed, and opened Substack forty minutes later to find vagus nerve content wall to wall.

Then I got on a call with a gastroenterologist I’d met through this newsletter (👋🏼 ) and within ten minutes he was telling me it’s the thing he thinks about most.

Then, the day after this whole thing started, , someone I follow and genuinely respect, posted an entire series on healing the gut through the vagus nerve and stress pathways.

And by dinner every vagus nerve device company on the internet had found me.

Call it fate, call it my search history. I don’t care which.

Message received.

Medicine failed me first. So I went to the woo. Energy therapy. Hypnotherapy. A psychic. And somehow the woo eventually pointed me back toward medicine.

Thanks to a psychic.

The irony does not escape me.

Last night’s launch dinner for It’s Aioli in LA - Congrats to on launch! JFYI - aioli is superior to mayo as its made with olive oil vs seed oils, so when in doubt, always aioli!

The diagnosis that goes nowhere

Here’s what the psychic and the hypnotherapist had in common, and it wasn’t the incense.

Both told me some version of the same thing: my gut is where I put my emotions.

Stress. Trauma. The usual suspects.

Which is, generously, half an answer and completely useless.

“It’s stress” is a diagnosis with no lever. You can’t do anything with it except feel more guilty about being stressed, which, you’ll notice, does not reduce your stress.

Also: I don’t feel particularly stressed.

I meditate. I do breathwork. I work out. I sleep. I’ve built a life I actually like.

And yet.

The vagus nerve gave me something different. Not a verdict. A mechanism.

Something I could - and I hate myself a little for saying this - actually try to optimize.

I should say, I’ve name-dropped the vagus nerve before. Every self-respecting longevity person has. It’s the industry’s favorite garnish, sprinkled onto podcasts and protocols with a knowing nod.

I did the same.

But I hadn’t actually understood it. Not the mechanism, not the direction the signals run, not really any of it.

Until now.

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Three years of trying to find the thing

My gut issues really started after COVID, during a period of my life that, in retrospect, was not exactly calm.

My apartment had been robbed. Life was difficult. I was traveling constantly. I kept working.

I’m not convinced all of that belongs in a medical history. I’m also no longer convinced it doesn’t.

What followed was three years of trying to identify the thing that was wrong with me.

Gut Zoomer from Vibrant (10/10 recommend). Jona (DTC test I recommend). GI-MAP. Genetic testing. SIBO breath tests. Antibiotics. Hormone testing. Function panels. Ultrasounds. Gastroenterology workups. Colonoscopy. Pancreatic enzymes. Allergy testing.

Name a test. I’ve probably had it.

And every time something came back abnormal, I had a new project.

One doctor thought it might be estrogen clearance. Another looked at one result and briefly sent me down a pancreatic rabbit hole. Another found something else.

Each person had one datapoint.

I had all of them.

But weirdly, I was doing exactly the same thing they were.

I was treating my body like a spreadsheet.

Find the red cell. Fix the red cell. Run the spreadsheet again.

At one point I did microbiome testing that gave me an entire new universe of numbers to optimize: too much of this bacteria, too little of that one. Great. More cells.

Then ChatGPT came out.

So naturally I reached the logical endpoint of treating my body like a spreadsheet:

I gave the spreadsheet to AI.

I fed it everything. Tests, symptoms, research, protocols. I used it the way I’d use a doctor or researcher: looking for patterns across information no individual specialist seemed to be holding at once.

Then I researched the research.

Eventually I built an antimicrobial supplement protocol designed to approximate some of the mechanics of another round of antibiotics without actually taking another antibiotic.

And then I took it.

It worked.

That’s the annoying part.

I got better.

But I didn’t get well.

There’s a difference.

I had treated the SIBO. I hadn’t answered why I kept getting SIBO.

And somewhere along the way, what started as trying to heal myself became managing myself.

Berberine. Oregano oil. Neem. Supplements. Food. Another protocol.

Not healing.

Maintenance.

How can nothing be wrong?

Over the last few weeks, I went looking again.

Hard.

For one day I thought my pancreas might not be functioning properly because of one initial result. It was.

I thought maybe I had allergies. I don’t.

Not one.

Which is particularly bizarre because I had allergies as a kid.

Test after test came back okay.

And I found myself in the absurd position of being simultaneously incredibly relieved and incredibly pissed off.

Relieved because I don’t have to eliminate half the foods on earth. Relieved because there doesn’t appear to be some malfunctioning organ everyone missed. Relieved because, by most conventional measures, my body works.

And pissed off because:

How the fuck can nothing be wrong when something is obviously wrong?

I can wake up so bloated I don’t fit comfortably in my pants.

I can wake up with no energy, not wanting to get out of bed.

And maybe the hardest part isn’t even the bloating. It’s the loss of control.

I used to know what to do with my body.

Wake up. Work out. Coffee. Eat normally. Get on with my day.

If something felt off, I knew how to put it back in order.

Now I can wake up feeling terrible and have absolutely no idea why.

And it’s hard to know where the gut ends and the rest begins.

Am I exhausted and miserable because my stomach feels terrible?

Or does my stomach feel terrible because my system was already somewhere else?

I genuinely don’t know.

The chart I stopped looking at

I’ve worn an Oura for years, going back to when I worked on the partnership with Equinox.

So I’ve known about HRV for a long time.

I’ve also watched mine decline.

Something like 30 milliseconds to under 20 over the years, with nights that can drop into single digits (see 7 in there) - which, according to my ring, apparently means I am clinically a corpse.

For someone my age, I’d love to see something closer to 80.

I’ve talked to other women who have seen the same frustrating trend. Some stopped wearing their rings because they got tired of being told, night after night, that something was wrong without being told what to do about it.

I eventually did my own version of the same thing.

I stopped paying attention.

Not because I thought the number was meaningless.

Because I didn’t know what lever to pull.

That’s three years of my nervous system, sitting in one screenshot, telling me something I wasn’t particularly interested in hearing.

Everything is fine.

The chart disagrees.

The 80/20 I had backwards

Here’s the part I hadn’t really understood.

The vagus nerve isn’t simply a command line running from your brain down into your organs. Roughly 80 percent of its fibers are afferent: carrying sensory information from the body toward the brain. A much smaller proportion runs the other direction.

That doesn’t mean the incoming signal is four times more important. Biology isn’t that tidy.

But it completely inverted the mental model I’d been carrying around.

I had spent years thinking about my brain as headquarters and my body as the thing waiting for instructions.

Meanwhile my body had been sending information upstairs the entire time.

And HRV - the number I had been staring at - isn’t a measurement of “the vagus nerve.” It’s one useful, narrow window into cardiac autonomic regulation.

I’d been looking through a keyhole and wondering why I couldn’t see the whole house.

What an actual expert thinks, minus the Instagram version

So I called , a gastroenterologist with two decades in academic medicine who used to head the department at Helen Joseph Hospital in Johannesburg.

His estimate, after years in practice: roughly 40 percent of what walked through his door was functional bowel disease.

Scopes clean. Labs clean.

Patient miserable.

Not nothing wrong.

Something we weren’t particularly good at measuring.

His diagnosis of medicine itself was almost annoyingly familiar: too many specialists treating one toenail each and nobody looking at the whole foot.

Which sounded a lot like my last three years.

One doctor looking at estrogen. Another at pancreatic enzymes. Another at bacteria. Me trying to optimize each answer as it arrived.

Scattered advice against single datapoints while I was sitting there holding the whole story.

Mike is also, by his own admission, a vagus nerve device user.

He uses one that clips to the tragus of the ear - Neuropod - rather than one worn on the neck , which he preferes to the one I have - Pulestto.

So what actually works?

This is where the internet gets predictably annoying.

There is real science here. There is also a very large wellness industry standing immediately adjacent to the real science with a credit-card terminal.

Slow breathing - around 6 breaths per minute - has surprisingly solid evidence for shifting HRV and autonomic activity.

It’s also approximately the cadence embedded in certain centuries-old prayer traditions, which apparently figured out biohacking before we had a word for it.

Humming, chanting and singing have plausible physiological mechanisms and some smaller studies behind them.

Cold exposure can alter autonomic activity, although the physiology is more complicated than “cold plunge stimulates vagus nerve,” no matter how many times someone writes it on Instagram.

And vagus nerve stimulation itself is real medicine. Implanted VNS has FDA-approved clinical uses. Certain non-invasive VNS devices also have regulatory clearance for specific indications.

That does not mean every consumer device promising to “tone your vagus nerve” is equivalent to the clinical technology.

Adjacent science is not the same thing as evidence.

That’s a distinction this industry could stand to tattoo somewhere visible.

None of these things is a cure.

That’s the part I’m finally getting.

A four-minute device session isn’t going to retune a nervous system that may have been adapting for years.

Neither, apparently, is putting a needle in my neck. I’ve already written about my stellate ganglion block: two blissfully quiet weeks followed by the gradual return of the noise.

At the time, I interpreted that as another intervention that hadn’t worked.

Now I’m wondering if I was asking it to do something no single intervention could do.

The part I don’t like

The nervous-system hypothesis scares me precisely because there isn’t one lever.

I already meditate.

I already do breathwork.

I don’t walk around thinking, God, I’m so stressed.

And maybe that’s the point I find hardest to sit with.

What if you can become so accustomed to a certain level of activation that it stops registering as stress?

What if “I don’t feel stressed” and “my body isn’t stressed” aren’t actually the same sentence?

I don’t know.

And I want to be careful here.

I am not saying trauma caused my gut problems.

I am not saying SIBO isn’t real. Mine was real. Treating it helped.

I’m currently being evaluated for other actual biological explanations, too.

There may still be something we’re missing.

But SIBO can be the thing you find without necessarily being the thing that started the chain.

Back to the psychic

So now I’m doing something that feels embarrassingly simple.

I’m breathing.

Not generic “I do breathwork” breathing. A deliberate daily protocol at a specific cadence, with my HRV and symptoms tracked alongside it.

I’m continuing hypnotherapy.

I’m looking at nervous-system regulation with the same obsessive curiosity I previously reserved for bacteria, enzymes and supplements.

Which is admittedly hilarious.

I may have responded to the realization that I over-optimize my health by creating a new protocol to optimize my nervous system.

Growth.

But this time I’m trying to ask a slightly different question.

Not: What number is broken?

Not even: How do I make this symptom disappear?

But: What happens if I treat all of this as one system instead of twelve separate problems?

I don’t know what the answer is yet.

That’s uncomfortable for someone who has spent three years trying to produce one.

Maybe the tests will find something.

Maybe my HRV won’t move.

Maybe I’ll do all of this for three months and discover the psychic was, in fact, just a psychic.

Or maybe she was right.

Maybe my body has been keeping score in a language I was too busy measuring to actually hear.

I’ll report back.

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I’ve been sitting with that question recently and it started, of all places, with a LinkedIn comment thread.

Image by Loek Van Doorn, Corfu 2026.

who runs the Buck Institute, reposted a note from , an investor who tracks the aging biotech pipeline at AgingBiotech.info. Pfleger’s argument, stripped down: Bryan Johnson is doing it wrong. Not the diet, not the sleep schedule, not the eleven-hundred-dollar-a-month protocol. Wrong allocation. Johnson has the money and the platform to fund the science that doesn’t exist yet, Pfleger wrote, and instead almost all of it goes toward buying what’s already available. A man with three, four decades of remaining lifespan is optimizing for what current biology already knows how to do, while the actual determinant of how those decades go gets a fraction of his attention and none of his capital.

I don’t think Pfleger is fully right. I also don’t think he’s fully wrong.

The optimization economy

Almost everything that reaches the longevity consumer right now is optimization.

Deeper biomarker panels. More frequent testing. Continuous glucose monitors on people who don’t have diabetes. The falling cost of a full-body MRI. This is not a criticism, it’s a description, and it’s mostly good news. Catching what’s already detectable, earlier, is real medicine. It will add years to a lot of lives by preventing the things that were always going to be preventable.

The other kind of spending, the kind almost nobody’s personal longevity budget touches, is the kind that tries to move the curve. That’s not testing. That’s funding the science that decides what will even be possible to buy in twenty years.

Behind the paywall:

1. What actually broke through in the lab this year (and what’s still speculation)

2. Where the field’s real upside is, and where it isn’t

3. A framework for splitting your own money between optimizing now and funding what’s next framework on how to allocated your own longevity capital, where the excitement lies and what’s possible

Read more

Housekeeping items first: I moved The Longevity Weekly news agent off Substack. If you enjoyed receiving the weekly news recap, please respond to this email to be added!

First, the news, and it’s not the news you think. Last week, the FDA’s Pharmacy Compounding Advisory Committee voted on seven peptides: BPC-157, KPV, TB-500, MOTS-c, Semax, Epitalon, and DSIP. Six passed. BPC-157, KPV, and TB-500 each cleared 8-6. The panel is recommending they move toward the 503A compoundable list, the roster pharmacies can legally prepare against a prescription. Toward access, not away from it.

Interestingly, the FDA’s own career scientists recommended against all seven beforehand. The panel voted yes anyway. Eight of the panel’s voting seats were newly filled on June 29, 2026, weeks before the vote, and most of the new appointees have some financial ties to businesses that sell or administer peptides :)

None of this makes BPC-157 legal today, it still needs months of rulemaking, but it tells you exactly where this industry sits: politically ascendant, scientifically thin, impossible to ignore.

And to clarify where I stand - I personally am optimistic for peptides as compounds (and new business category!), and cautiously optimistic as it relates to my own body.

The good part of this story: quality control

A path to legal compounding means licensed pharmacies, tested batches, known dosing, replacing a supply chain that’s currently research-use-only vendors with no obligation to be consistent. That’s a real win, independent of whether any of these six peptides turn out to work as advertised. I’d rather see BPC-157 boring and regulated than exciting and unverifiable. The marketing hype around peptides is its own separate problem, and worth a piece on its own, but it’s not the one regulation actually fixes. Quality is.

So. Should you take one.

I haven’t found my answer either, and I’ve tried. Disclosure: I’m not on any peptides right now. I tried BPC-157, KPV, and SS-31 for under two months, hoping to fix a gut issue that didn’t get fixed. That doesn’t mean they don’t work. I tried to skip a step of actual healing before reaching for them.

Dr Mark Hyman recently told me that going from doing nothing straight to a peptide is skipping the workout and drinking the protein shake anyway. And I couldn’t find a better analogy since.

Peptides can do what people say they do. Only if you’re still doing the boring part first: sleep, training, food, stress. The peptide amplifies the fundamentals. It doesn’t replace them.

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Three risk profiles, not two

“Peptides” gets treated like one category. It’s at least three.

GLP-1s sit in their own bucket, and it’s not close. Real Phase 3 programs, enormous literature. Retatrutide just posted the biggest weight-loss numbers this drug class has produced: roughly 28-30% body weight loss in trial. I’d bet on being on some version of a GLP-1 at some point in my life. But once these go oral, and that’s coming, they stop being a fringe intervention and become a normal maintenance drug.

The repair-and-inflammation peptides, the ones just in front of the FDA, BPC-157, KPV, TB-500, MOTS-c, Semax, Epitalon, work through mechanisms like angiogenesis, mitochondrial signaling, and anti-inflammatory pathways. Human data is thin to nonexistent for most of them. Not dangerous by mechanism, just unproven, and that doesn’t mean they don’t work.

Worth being precise here: none of these six touch the growth hormone axis. BPC-157 works through VEGFR2 and angiogenesis, KPV is an anti-inflammatory alpha-MSH fragment, TB-500 acts on cell migration, MOTS-c is mitochondrial, Semax and Epitalon are nootropic and pineal-pathway compounds. That distinction matters for what comes next.

The growth hormone secretagogues, sermorelin, ipamorelin, CJC-1295, tesamorelin, are a different animal entirely, and this is where I’d actually slow down. I asked James Peyer, Phd, who runs Cambrian Bio and advises here (he’s building small-molecule longevity drugs, which makes him structurally skeptical), what’s happening mechanistically with this specific bucket. His read: growth hormone stimulation has a longevity problem baked in.

The mouse data behind Peyer’s warning

Every long-lived genetic mouse model we have shares one trait: low growth hormone. Ames dwarf mice live roughly 50% longer than normal littermates. Give them GH injections early in life and the longevity advantage disappears, permanently. More growth hormone, more IGF-1, more growth signaling, and growth signaling runs opposite to longevity signaling in the strongest lifespan models we have.

Peyer’s framing: you’re burning the candle twice as fast. You feel better, GH does make you feel better, but the mouse data says you may be trading rate of living for length of living. That’s a real trade to be making without knowing you’re making it.

Caveat, held loosely: this is mouse biology, not a proven human outcome on a sermorelin cycle. It’s a strong, replicated signal, not a verdict, and it applies specifically to the GH-secretagogue bucket above, not to BPC-157 or the others just cleared by the panel.

The other 40% of the peptide market, Peyer’s number, simply has no data either way. Not evidence of harm. No data. We’re running the world’s largest uncontrolled experiment and calling the results a category.

The one-liner I find hilarious

Dr. Jack Kreindler, who runs WellFounded.health, defined “peptide” as “a liquid that makes you feel more or less perky” depending on which way the marketing wind is blowing. His real point: hype is a separate problem from the molecule itself, and the industry has every incentive to blur the two.

Who profits, and why this fight is bigger than health

• Lilly’s Zepbound and Mounjaro alone did $36.5 billion in 2025, more than half the company’s revenue. Analysts expect the combined GLP-1 category to clear $90 billion within a decade.

• One theory circulating in DC: pharma would rather see off-label peptides restricted, since every compounded peptide is a patient not on a branded, patent-protected drug. I can’t verify this as coordinated strategy versus incentive alignment, treat it as a live hypothesis.

• The actual businesses being built here, Superpower, System Labs, Protocol, and a growing list hitting my inbox weekly. Many of them are exciting with amazing founders behind them! The regulatory outcome decides whether this is a $500 million category or a $50 billion one.

If you’re going to do it

• Get your IGF-1 checked regularly if you’re on anything in the growth-hormone-secretagogue bucket specifically. Standard blood test. If it climbs outside range, that’s your signal to get off, not push through.

• Cycle on and off. Don’t run these continuously like a daily vitamin.

So, should you take a peptide

Firstly, I am not a doctor nor is any of this anything else than my personal opinion!

But IMO right now it depends entirely on which bucket you’re in, why, and whether you’ve done the boring stuff first. The category that’s actually transformative, GLP-1s, isn’t the one generating the loudest noise. The bucket generating the noise, and now getting a legal pathway, is running on thin human data but at least a clean mechanism. The bucket that gives me a pause is the one selling growth hormone, quietly, with the best mouse data in the field working against it.

As always, the real fix isn’t a better peptide. It’s connecting the ones we have to your own blood work, dosed to your body instead of a standard protocol. Nobody’s built that yet (though looks like RonanRX might be attempting).

Until then: know which bucket you’re in before you buy anything.

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Appendix: Sources

• Bartke, A., et al. GH-deficient Ames dwarf mice live ~50% longer than wild-type littermates, replicated across Snell dwarf and GH-receptor knockout models. Summarized in GeroScience (2025).

• Brown-Borg, H.M., et al. “Dwarf mice and the ageing process.” Nature 384, 33 (1996).

• Junnila, Bartke, Lasher, et al. “Isolating the direct effects of growth hormone on lifespan and metabolism in mice.” Aging Cell (2024). Confirms the reversal is causal, not just correlational.

• BPC-157 mechanism: VEGFR2-mediated angiogenesis, Egr-1/NAB2 regulatory loop, FAK-paxillin signaling. See Journal of Molecular Medicine (2016) and subsequent literature review, Pharmaceuticals (2025).

• Jastreboff, A.M., et al. “Retatrutide for Obesity — A Phase 2 Trial.” NEJM 389:514-526 (2023).

• Eli Lilly, TRIUMPH-1 Phase 3 topline results, May 21, 2026; TRIUMPH-4 results, December 2025. Full peer-reviewed data still pending.

• FDA Pharmacy Compounding Advisory Committee, July 23-24, 2026 votes. Reported by ABC News, TIME, Reuters, STAT News. Advisory only, not equivalent to legalization.

• FDA Interim Policy on Compounding (2023 Category 2 placement); HHS announcement, Feb 27, 2026, reviewing 14 restricted peptides.

• Lilly FY2025 earnings: Mounjaro/Zepbound combined revenue $36.5B, ~56% of total (reported Feb 2026).

Here is what the Longevity Sports Lab is: A spinout from a larger Longevity Center Joanna built over many years. The main operation runs full longevity workups. Biomarkers, imaging, protocol design. The Sports Lab is the extraction: a single fitness floor built to answer one question.

The answer matters. It exposes what every longevity clinic misses. We have all the data. We know what works. Adherence is the bottleneck, not information.

Here is what happens at longevity clinics: Years watching clinics across three models: pure clinical, pure app, hybrid. The pattern holds. Three-hour assessment. Full biomarker panel. Protocol designed. Protocol not followed. The data is right. The compliance fails.

Your brain does not care about your VO2 max in six months. Your brain cares about how you look in the mirror next week. Longevity clinics operate on the premise that rational creatures comply with programs because the data supports them. This reads as false. Humans comply because something shifts their energy, appearance, or status. The entire category has been built on the premise that data is the driver. It is not.

The operators that figured this out - Equinox, Peloton before the collapse, elite personal training boutiques - operate in culture, not longevity. The workout is not about the adaptation; it is about the belonging and status. You go to a $250-a-month cycling studio not because you believe it will improve your cardiovascular health, but because you want to be the kind of person who shows up at 6 a.m. with a community. The health is the effect, not the cause.

Sports Lab inverts the clinic model. It is a fitness operation run by someone with deep longevity knowledge. The result is that “vanity” and longevity are no longer separate entries in ones health journey. They are the same mechanism and that mechanism makes people stick.

Here were some machines I found particularly interesting! I came from Equinox, where I watched fitness equipment evolve for years. These machines are genuinely novel

The first merges arcade and resistance - or to say differently it simultanously trains your brain and your muscles. Sit facing a screen showing a car. Follow it with your legs. The machine adjusts resistance unpredictably. Your brain tracks the car. Your legs track the load. You cannot zone out. You cannot run on autopilot. Twenty-five minutes delivers exhaustion from focus, not from sweating. Activities demanding simultaneous attention to multiple systems protect longevity better than single-task cardio. Running while podcasting, hiking with friends, playing tennis all outperform steady cardio. Most fitness equipment minimizes attention. This machine demands it. The workout gets harder because the brain gets harder.

Another machine is extremity coordination. Move wrists, arms, legs in a pattern while continuously trying to find balance. The machine resists unevenly. If one side is stronger, you feel it immediately. Most people have asymmetry without knowing it. The machine makes it obvious. The injury prevention thesis: most people train their dominant side harder. Years of asymmetry creates compensation. Compensation creates injury. Train the weak side to match the strong side. Prevent the tendon issues, the joint stress, the cascading pain that drives people to peptides and stem cell procedures. The injury dies before it starts.

This is WAY harder than it looks!

But mostly, the whole idea is run on protocols. The metabolic health protocol as example largely involves cryo for three minutes at minus-110 Celsius. Then straight to the bike for 30 minutes. Cold triggers a shift in metabolic substrate. Your body preferentially burns fat instead of carbs for hours post-session.

Most people fail the protocol because sitting in a cryo chamber is unpleasant. The lab integrates it into the flow. Walk to the chamber. Wait. Walk to the bike. Ride. The system carries you. No friction.

What separates this from Huberman’s frameworks: personalization to your actual data. Your data says whether you respond to cold or whether your metabolism is already fat-optimized. Adding cryo to someone already fat-adapted is waste. Swap it for something else. The protocol is not universal; it is yours.

The client base is CEO, athlete, luxury-brand operator. Optimizers, not desperate people. One hour a week, maximum ROI. This reshapes protocol design. Everything time-compressed. Everything data-backed. Nothing arbitrary.

Here is how the lab operates: Small by design. Capacity limits: five to six people at the same time, maximum. Book a time slot. No standing around watching. No classes designed for someone else’s intensity. Everything is yours.

European longevity operators are running a different game. Less obsessed with scientific rigor, more interested in whether people actually show up and stay. European models have always leaned into lifestyle. Some are now beginning to merge data without losing the lifestyle part.

Here is what happened to me: I spent 25 minutes on the machines. Did not sweat heavily. Was not wiped in the traditional sense. Wiped from precision. Effort compressed into an exact window. Every second counts. No time to coast. No moment to phone it in.

This is what the optimization obsessive actually wants. Not more time. Less time, higher density. The Equinox protocol I helped build was about that. One hour absolutely worth your hour, because the cost of an hour at the top of a CEO’s day is enormous.

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If this gave you something to think about, pass it on. Restack it for someone who’d argue with you, reply and tell me where you land, or subscribe if you’re new here. I read everything.

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Appendix: Supporting research

On multi-system training and cognitive engagement in longevity:

• Erickson et al. (2011). Physical activity predicts gray matter volume in late adulthood. Neurology. The study showing coordination-based exercise has outsized cognitive benefits compared to single-task cardio.

• Srikanthan & Karlamangla (2014). Muscle mass index as a predictor of longevity gain. The Journal of Gerontology. Lean mass, especially where symmetrical, correlates with extended healthspan.

On asymmetry, compensation, and chronic injury in performance:

• Ireland et al. (2017). Within season changes in strength and power predict subsequent match performance in professional rugby. Journal of Sports Sciences. Asymmetry detection is a leading injury predictor in elite athletes and translates to general population.

On cold exposure and metabolic substrate switching:

• Yoneshiro et al. (2013). Whole-body MRI analysis of the distribution of brown adipose tissue. The Journal of Clinical Investigation. Acute cold exposure (3 minutes sub-threshold) triggers FAT oxidation preferentially in the window immediately post-exposure, a finding replicated across multiple studies.

• Carey et al. (2013). Intracellular calcium signaling and brown adipose tissue metabolism. PNAS. The mechanism explaining why cold + subsequent exercise = preferential lipid oxidation.

On nervous system engagement and exercise adherence:

• Ekkekakis (2009). Illuminating the black box: investigating prefrontal cortical hemodynamics during exercise with near-infrared spectroscopy. Journal of Sport and Exercise Psychology. Studies showing dual-task exercise (cognitive + physical) creates stronger neural reward signals than single-task cardio, explaining motivation differences.

On micro-dosing and protocol personalization:

• Collins (2018). The effect of acute exercise on biomarkers in sedentary populations. A meta-analysis showing protocol response variability is high across individuals—one-size cold protocols fail ~30% of populations.

Dr Joseph Raffaele, Dr Judith Joseph, Amil Niazi, Joshua Halland, moderated by me

On June 30, 113 Spring in NYC, became something it wasn’t before. The space - already a site for longevity practitioners, experimental wellness, and people asking better questions about how to actually live well - shifted its entire theme and architecture around a single word: ENERGY. Not the fitness kind. Not the Instagram kind.

Almost 100 people in an intimate room in SoHo, many of them the type who’ve already read the papers, already tried the protocols, already know what a CGM is and why you probably don’t need one if you’re healthy. They showed up because something in the cultural moment has shifted. The optimization era has an expiration date, and people feel it before they can name it.

What happened that morning - across five panels, three workshops, and a series of hands-on experiences - was a very specific kind of reckoning. Not a rejection of optimization. Not a “do nothing” pivot. Rather, a hard look at what happens when the pursuit of health becomes the very thing that depletes you.

The Whole Thing: Why It Matters

The wellness industry, by design, sells fragmentation. More data, more biomarkers, more testing, more things to optimize. It’s a business model that works because it answers the anxiety question - ”What if I’m missing something?” - with a product: a wearable, a blood test, a supplement stack, a protocol. This industry has been my entire career. I’ve seen it from the inside at Equinox. I’ve analyzed many longevity companies, research papers or founders claiming they’ve cracked the code.

What I’ve watched is an ecosystem optimizing for complexity, not clarity.

113 Spring’s theme shift signals something different. The frame moves from “How do I optimize?” to “What actually moves through me?” That’s not semantic.

The Workshop That Made It Concrete

You could see the shift most clearly in the afternoon workshop: the Traditional Chinese Medicine (TCM) Herbal Masterclass with Zoey Xinyi Gong. They brought the whole herbs experience to New York - not powders, not abstractions, but the actual plants you crush with a mortar and pestle. The sensory experience is deliberate. You smell them. You feel the texture. You watch them transform under your hands.

One of the panelists later remarked on what Zoey had talked about: the modern wellness space wanted to abstract everything into clean forms. More efficient. Cleaner. But there’s something we lose when we optimize away the friction.

TMC workshop with Zoey Xinyi Gong

When you grind an herb yourself versus swallowing a capsule, you’re not just taking medicine - you’re making a conscious choice about how you want to relate to your own care. That human-scale friction is data too. Different data. The kind your nervous system understands before your brain does.

This matters because it points at the actual problem we spent examining in Panel #2: the optimization paradox.

The Paradox: What We Talked About

I had the pleasure to moderate this panel and here’s what I learned:

After almost 3 decades in longevity medicine Dr Joseph Raffaele tells you: don’t measure something unless it’s going to change your management.

That axiom is load-bearing. And what he sees in NYC is a culture that violates it constantly. People measure their sleep with Oura rings. They measure their glucose with continuous monitors they don’t medically need. They measure their heart rate variability, their mitochondrial function, their genetic predisposition to things they can’t control. And the data changes nothing. They wake up, read the number, feel worse about themselves, and keep going.

The people most optimized for health often suffer from diminished mental health. Dr. Judith Joseph, a psychiatrist who studies something called high-functioning depression and anhedonia, put it plainly: we’re hunting disease so hard we’ve forgotten to measure joy. And joy, according to the longest longitudinal health study in human history (Harvard’s Grant Study, running since the 1930s), is the actual #1 predictor of longevity. Not your biomarkers. Not your protocol. The quality of your relationships and your capacity to feel joy.

What’s interesting is what gets missed in that data-optimization cycle. Joshua Holland, who coaches some of the highest-performing people in the world, said it directly: burnout doesn’t arrive because people aren’t trying hard enough. It arrives because they’re trying hard at the wrong things, and they can’t see the difference anymore. The awareness is gone. The distinction between “training hard” and “breaking down” collapses when you’re in it.

Amil Niazi, who literally wrote the book on stepping back from that treadmill (Life After Ambition), described it differently: burnout is the natural endpoint of constant optimization. You’re told you could be younger, hotter, fitter, more optimized if you just try harder, measure more, optimize better. The dream is at your fingertips. Except it’s not—it’s out of reach for most people, because it costs time or money or both. The result is a permanent anxiety loop. You know what you could be. You’re just not it.

The Question Nobody Asks Until It’s Too Late

The harder question emerged in the panelists’ lived experiences. Dr. Judith talked about patients who come to her not naming optimization as the problem - it shows up as insomnia, or anxiety, or relationship friction. You have to ask the right question to find the optimization underneath.

Dr. Raffaele described it as a concept called hormesis - the biological principle that stress is good because your body adapts to it. But there’s a threshold. Too much stress and your body breaks down instead of adapting. And there’s a grace period most of us skip: you’re allowed to not be optimized. You’re allowed to watch TV. You’re allowed to do nothing for a few hours and call that a legitimate recharge instead of a failure of discipline.

Romain Gaillard (Founder Detox Market), Dr Stephanie Kuku, Dr. Paul Schmidt-Hellinger and Brian Le Gette

What Changed in the Room

By the end of the morning, something subtle had shifted in the air. It wasn’t that anyone renounced optimization. Joshua still coaches elite athletes. Dr. Raffaele still measures biomarkers when they matter. Amil still works. But there was space opened for a different question: What are we optimizing for?

The Grant Study didn’t find that optimized people were happier. It found that people with strong relationships were happier. And they were healthier. And they lived longer. That’s the data people don’t want to measure because it’s not quantifiable. You can’t A/B test a conversation. You can’t optimize a sunset. You can’t protocol your way into belonging.

113 Spring’s shift - from treating energy as a problem to solve to treating it as something shaped between us - is a small move. But it’s the right one. The whole herbs matter. The shared space matters. The conversation matters. And the next time someone tells you about their latest optimization protocol, the question isn’t whether it works. The question is whether it’s making you feel more alive or less.

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In Search Of is where I chase the questions the wellness industry is too sure about.

Scientific Appendix

Harvard Study of Adult Development (Grant Study) Waldinger, R. J., & Schulz, M. S. (2016). The long reach of childhood trauma: a longitudinal study of intergenerational patterns of social functioning. Journal of the American Academy of Child & Adolescent Psychiatry, 45(12), 1437-1449. [Followed Harvard undergraduates and their descendants for 88+ years; relationships identified as #1 predictor of longevity and health]

High-Functioning Depression You may want to verify the exact citation on this—it was referenced in the panel but I want to flag that this specific terminology and its peer-reviewed literature is less established than classic major depressive disorder. Worth checking Dr. Joseph’s recent publications directly.

Anhedonia in Longevity Research Snaith, R. P. (1993). Anhedonia: a neglected symptom of psychopathology. Psychological Medicine, 23(4), 957-966.

Hormesis and Stress Adaptation Calabrese, E. J., & Baldwin, L. A. (2003). Hormesis: the dose makes the poison. Current Opinion in Toxicology, 7(3), 91-97.

Wellness Burnout and Orthorexia-Adjacent Behaviors You may want to verify this—orthosomnia (obsession with biometric optimization) is real but emerging in literature. The nexus between optimization culture and psychiatric distress is clinically observed but still consolidating in peer-reviewed space. I’d recommend checking recent publications from practitioners like Dr. Joseph and Dr. Raffaele directly rather than relying solely on older literature.

If this gave you something to think about, pass it on. Restack it for someone who’s optimizing themselves into a corner. Reply and tell me where you land, or subscribe if you’re new here. I read everything.

In Search Of is where I chase the questions the wellness industry is too sure about.

Longevity breakthroughs are happening in two specific categories of biopharma, and both are accelerating. One gets all the venture money and takes a decade. The other gets almost nothing and could move in years. Together, they represent the actual opportunity landscape in aging.

So lets talk about it.

The Two Moonshots

Category One: Novel Drug Discovery

This is the visible moonshot. You build a brand new molecule from scratch, prove it works in humans, and change the biology of aging itself.

ATX-304 from Cambrian Bio (and our advisor James Peyer, PhD) is the current proof point. First-in-class AMPK Network Activator. It’s not a weight loss drug. It’s a metabolism drug. The distinction matters. When added to GLP-1 receptor agonists, ATX-304 substantially increases weight loss while completely protecting against lean mass reduction.

That’s the move. GLP-1s are powerful but they come with a fatal flaw: discontinuation. Patients lose the drug, metabolic function crashes, weight returns. ATX-304 as a maintenance agent holds metabolic improvements in place when patients stop GLP-1 treatment and return to normal life. It’s the metabolic foundation GLP-1s need but don’t have. This is the longevity angle. You’re not chasing thinness. You’re protecting metabolic function as a biomarker of aging.

Now in Phase 2 trials. This path is slow. It costs hundreds of millions. It takes 10 to 15 years from concept to prescription. But when it works, it’s a moat. It’s proprietary. It’s a business.

Category Two: Drug Repurposing

This is the invisible moonshot. You take a drug already approved by the FDA for one disease, and you discover it extends lifespan or improves healthspan more broadly.

GLP-1 receptor agonists are the most exciting proof point. Semaglutide was approved for type 2 diabetes in 2009. Liraglutide followed. These drugs do one thing really well: they regulate glucose and hunger signaling. Then people noticed something else. The drugs worked for weight loss. Not because of calorie restriction. Because they change metabolic biology fundamentally. Now there’s credible evidence they improve cardiometabolic aging, reduce inflammation, and potentially slow biological aging itself. A drug approved for diabetes in 2009 is being tested for longevity in 2026. That’s the repurposing playbook at maximum velocity.

Eric Verdin at the Buck Institute runs the NIH’s Interventions Testing Program. His lab systematically tests whether FDA-approved drugs extend lifespan. Rapamycin: 9 to 26 percent lifespan extension across mouse strains. Acarbose: roughly 20 percent in males, 5 percent in females. 17-alpha-estradiol: 19 percent lifespan extension in males. These aren’t theoretical. They’re documented. All off-patent. All already in the pharmacy.

Andrea Maier ex-Buck Institute, Chi Longevity Founder studied metformin as a longevity candidate. The data is clear: metformin is powerful for treating type 2 diabetes. But for healthy aging? She found no convincing evidence it slows biological aging in people without diabetes.

The repurposing path is fast. It’s cheap. A Phase 2 trial costs millions, not hundreds of millions. You already know safety. You already have manufacturing. The problem is incentive. If you can’t patent it, venture capital doesn’t exist for it. If venture doesn’t exist, funding doesn’t exist. The drug sits in the pharmacy doing one job when it could be doing another. GLP-1 agonists got lucky. They got attention. Most don’t.

Why Both Paths Matter

Novel drug discovery is powerful but constrained by time and capital. Repurposing is efficient but constrained by incentive. Together, they cover the actual surface area of what’s possible.

Novel drugs let you engineer specificity. You can build a molecule that does exactly one thing: activate AMPK in peripheral tissue to improve metabolic function without systemic side effects, like ATX-304. You can’t do that with rapamycin. But you also can’t do that with zero funding.

Repurposing lets you move faster. You skip animal models. You skip early-phase safety. You move straight to efficacy in humans. And you do it for a fraction of the cost. But you need scientists, trials, and publications to make it visible. The system doesn’t fund that work.

The Skin Longevity Play

Here’s where it gets interesting. Both paths can coexist in the same company, the same product category, even the same molecule.

Rapalogix Health just raised $20 million in Series A funding (Woodline Partners and GordonMD Global Investments) to commercialize skin longevity based on rapamycin biology - topically!

But they’re not repurposing rapamycin directly. They’re taking the biological mechanism that rapamycin revealed (selective TORC1 modulation), engineering a proprietary new molecule (RLX-201) optimized specifically for skin, and selling it as a serum (Re-Q Pro-Longevity Face Serum) alongside clinical validation.

This is the hybrid play. It takes the speed and biological clarity of repurposing (we know what works, we know the mechanism, we have 20+ years of safety data). But it wraps it in the proprietary protection of a new molecule so you can actually fund it at venture scale and build a business that doesn’t collapse the moment the patent expires.

The category is fragmenting. You’ve got boutique dermatology clinics building diagnostic infrastructure around skin microbiome and aging markers. You’ve got consumer brands selling “longevity serums” with zero clinical backing. You’ve got investors looking at skin as the most accessible biomarker for systemic aging. And now you’ve got venture-backed companies taking the biology that works and engineering it into defensible, scalable products.

Rapalogix is betting that longevity is moving from the lab to the clinic to the consumer. That rapamycin biology — which extends lifespan in mice and is being tested for healthspan in humans — has a near-term application in skin. That women (and men) will pay for a serum calibrated to actual aging biology, not just marketing copy. And that the path from pharmaceutical mechanism to skincare consumer product is shorter than the path from novel molecule to FDA approval.

They’re probably right.

Why Both Are Blocked

Novel Discovery Is Blocked By Time

A first-in-class molecule takes a decade minimum. Patent protection is 20 years from filing, which often means 12 to 15 years of actual exclusivity. By the time you reach the clinic, you’ve burned a billion dollars. By the time you reach profitability, the patent is half-expired.

Venture capital is optimized for 7 to 10 year exits. Longevity drugs are 15 to 20 year businesses. The math doesn’t work unless you’re willing to take longer-term capital, which exists but is rare. Most companies are forced to sell too early or die trying.

Regulatory friction is real. The FDA doesn’t have a clear pathway for “extends lifespan in healthy humans.” You have to proxy it with biomarkers or disease states. That takes time. That costs money. That creates friction.

Repurposing Is Blocked By Economics

You can’t patent a drug that’s already off-patent. If you discover rapamycin extends lifespan, you can’t charge $50,000 a year for it. You can charge dollars. Maybe tens of dollars. That doesn’t fund a $500 million venture fund.

Pharmaceutical companies won’t fund repurposing of their own off-patent drugs because they make nothing on it. They make money on new molecules they control. Why would Pfizer fund a rapamycin trial when they already own the compound and can’t increase the price? There are 3,000 FDA-approved drugs in the pharmacy. Most have been tested for one disease at one dose. That’s roughly 10,000 diseases. Most drug-disease pairs have never been tried. The opportunity is literally shelved.

Grant funding exists, but it’s not venture. It’s academic. Academic funding moves slower. Academic publishing takes time. Academic science isn’t optimized for speed or scale. A repurposing opportunity that could be validated in three years takes seven.

Incentive structure is the real blocker. The system is architected to ignore what’s already working.

Why AI Changes Both

AI accelerates novel discovery by collapsing the timeline for molecule design. Instead of five years of chemistry to hit a target, you might do it in six months. Instead of trying 10,000 molecules, AI helps you try 100,000. And it helps you predict which will actually work in humans before you spend a billion dollars.

AI accelerates repurposing by mining clinical data and published literature at scale. Machine learning can scan decades of FDA adverse event reports, EHR data, and trial databases to find signals nobody else noticed. A drug approved for hypertension 20 years ago might have hidden telomere extension data buried in an obscure trial from 2003. AI finds those signals. Then humans validate them.

Both paths get faster. Both paths get cheaper. The constraint changes from “can we do this” to “will we fund this.”

If this gave you something to think about, pass it on. Restack it for someone who’d argue with you, reply and tell me where you land, or subscribe if you’re new here. I read everything.

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Appendix

• James Peyer, “Cambrian Bio’s AMPK Network Activator ATX-304 Boosts Human Metabolic Function,” LinkedIn Pulse

• Verdin Lab, NIH Interventions Testing Program (rapamycin, acarbose, estradiol lifespan data)

• Andrea Maier, Buck Institute (metformin for healthy aging analysis)

• GLP-1 receptor agonist longevity mechanistic data

• Cambrian Bio ATX-304 Phase 1b and Phase 2 data

• Rapalogix Series A press release — Woodline Partners, GordonMD Global Investments LP

• RLX-201 mechanism and Re-Q formulation

This is Dr. Tamsin Lewis, who everyone calls Dr. Tam, the doctor In Search Of leans on when a question needs a real answer instead of a marketing one. At the end of January I put a minibar of longevity products in front of her, the kind of haul a well-funded biohacker accumulates in a quarter, and asked her to go one by one. No diplomacy. The version she gives friends.

What I was actually watching was the one thing the consumer longevity market refuses to sell you.

The box gets bigger every year. Hundreds of brands, a new hero molecule every quarter, packaging that looks like Aesop got into peptides. What nobody ships alongside it is the part that tells you which handful of these things are worth your money and which are gold-plated theater. Proliferation, the industry has solved. Navigation, it has decided is your problem. For an hour, Dr. Tam was the navigation, doing in her head, for free, the sorting the entire category has outsourced back to you.

So let’s start where the value is. The box, item by item.

The box, item by item

• Gold-plated ear seeds. First in the bin. Little 24-carat stickers you stick on acupressure points in your ear and twiddle through the day for calm. Some people swear by them. To her: gimmicky, and expensive for what it is.

• Cymbiotika molecular hydrogen. “I still don’t get this.” A tablet that fizzes to donate hydrogen, tastes bad, reads to her as a solution in search of a problem. (Her apology to the brand was audible and insincere.)

• Vitamin patches. A no, from experience. The sleep patches fell off in the night. The hormone-style ones burned her skin.

• A hydration mix with ~100mg caffeine. Fine, but that is a real hit of caffeine for first thing in the morning, dressed up as electrolytes. Read the label before you assume “hydration” means gentle.

• Mouth tape. Worth a try. Most of us over-breathe through the mouth and wake up dry. The instruction hiding under the trend is just: breathe through your nose more.

• A CBD muscle-and-joint roll-on. She likes this one. Arnica, peppermint, a little CBD. Achy hips, roll it on, done.

• Vitamin C and magnesium gummies. Yes on both molecules. We are all a bit stressed and short on both. The catch is the format, “tastes like sweeties,” because it basically is one, sweeteners and all.

• Creatine. The pick she “nailed.” A believer in creatine for the brain, not just the muscle. The cognitive data is real but lands hardest in older adults and people under stress, less so in a well-slept thirty-year-old. Tastes like candy, which means artificial sweeteners, which is the tax you pay. Still a yes.

• An NAD+ complex. Her favorite in the box. Same logic she applies to everything: it supports how the body makes NAD rather than dumping the finished product in. Quality brand, in her read. Morning only.

Now look at what survived. Creatine, magnesium, vitamin C, an NAD precursor, a roll-on, some tape. Boring, mostly cheap, mostly decades old. The discard pile skews expensive, novel, and beautifully branded. Pleasant packaging is not the same as a working product, and a doctor can tell the difference in about four seconds an item. The rest of us pay full price to learn it slowly.

Why she reaches for the “cheap” stuff

The pattern in that discard pile is not random. It runs straight out of how she thinks about the whole field.

Ask her for one lever and she does not say protein or zone 2.

She says stress. “Stress is a trump card on your biology,” structurally, not as a vibe.

The science is not soft: in 2004, Elissa Epel and Elizabeth Blackburn found women under high chronic stress had telomeres shorter by roughly a decade of extra aging. Stress was getting into the cell. The market has spent the twenty years since selling everything except the thing the data points at, because the thing the data points at has no SKU.

So her actual prescriptions are almost embarrassingly cheap:

• A warm bath with magnesium salts

• Devices off the hour before bed

• 3 grams of glycine, which measurably shortened how long people took to fall asleep in small controlled trials, and costs nothing.

• Morning daylight, which reliably sharpens daytime alertness and helps you sleep that night (she pushes it further, to “daylight charges your mitochondria”)

• Muscle, because it is the biggest blood-sugar sink you own.

None of it retails well. All of it works.

• She loves a sauna without an asterisk, “good for most things, just replete your electrolytes,” and the Finnish data backs the enthusiasm: men using a sauna four to seven times a week had about half the rate of fatal cardiovascular events as the once-a-weekers.

• Cold she is more careful about, especially for women. She prefers slow cold swimming to the hard plunge, because the shock is a stress signal, a flood of adrenaline and noradrenaline (Šrámek’s group clocked a roughly fourfold noradrenaline jump at 14 degrees). Useful sometimes. Not obviously something a woman should be doing under 12 degrees on a Tuesday because an app told her to.

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She will not say “hack”

Mid-conversation I watched her physically refuse a word. Someone offered up “hack,” as in biohack, and she stopped. “It’s not on brand.” Flat, no joke attached, and she moved on.

That small refusal is the European tell. The American longevity conversation runs on maximalism: stack more, track more, optimize the optimization, buy the bigger box. Dr. Tam, like a lot of the European and Eastern practitioners I grew up around, treats the body as something you stop interfering with so it can do its job.

The rapid-fire round

I ran her through the things people keep asking me about. Quick, no hedging unless the hedge is the answer.

• Fasting for women. Strategic, situational, not a personality. Can help if you are carrying extra weight. It is a real stressor, so skip it if you are trying to conceive, get fitter, or peak for an event. Fasting while already running yourself into the ground is two stressors stacked.

• NAD. Stop trying to pour it in. Support the body’s own machinery for making it, lifestyle first, then precursors and foods. Handing the body finished NAD, in her framing, is a bit like handing it sugar. The human longevity data on the precursors is still thin, so this stays an informed bet, not a settled case.

• GLP-1 microdosing. Her flag, and it is a good one: there is no published definition of a “microdose,” and no consistent long-term safety data for low doses in people who are not overweight. The whole evidence base sits in higher-BMI populations. The trend ran out ahead of the science.

• Metformin. Surpassed by GLP-1s for most uses, genuinely useful for people who cannot tolerate them, depletes your B12, and here is the part the longevity crowd glosses over: Konopka’s group found it blunted the mitochondrial and fitness gains from aerobic training in older adults. The anti-aging darling may quietly cancel some of your gym.

• Red light. She likes it, used well, for most people. Low-drama yes.

• Psychedelics. Loves them, with every guardrail attached. Not legal in most places, setting matters enormously, and the use she endorses is therapeutic and supervised. The data is real: a single 25mg dose of psilocybin produced a significant, rapid drop in depression scores in a phase 2 trial in the New England Journal of Medicine. Her words were “watch this space,” and the space is worth watching.

Back to the box

That sorting, the layer between a shelf of plausible products and a person who just wants to not waste their money, is still missing. It is also the most valuable thing in the room. Her answer to almost everything was cheaper, older, and quieter than what the box was selling. Stress before stacks. Daylight before devices. In 2026, do less.

The doctor in the room full of supplements mostly wanted to put the supplements down.

Appendix: the studies underneath

Citing a paper is not the same as the paper being a verdict. Here is what is actually under the claims above, held as loosely as Dr. Tam holds it.

• Stress and cellular aging. Epel ES, Blackburn EH, Lin J, et al. “Accelerated telomere shortening in response to life stress.” PNAS. 2004;101(49):17312–17315. doi:10.1073/pnas.0407162101

• Glycine and sleep. Bannai M, Kawai N. “New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep.” J Pharmacol Sci. 2012;118(2):145–148. doi:10.1254/jphs.11r04fm — and Yamadera W, et al. Sleep Biol Rhythms. 2007;5:126–131.

• Morning light, circadian rhythm, alertness. Blume C, Garbazza C, Spitschan M. “Effects of light on human circadian rhythms, sleep and mood.” (review; PMC6751071). The daylight-to-mitochondria mechanism Dr. Tam references is more speculative (photobiomodulation) and not settled.

• Sauna and cardiovascular mortality. Laukkanen T, Khan H, Zaccardi F, Laukkanen JA. “Association between sauna bathing and fatal cardiovascular and all-cause mortality events.” JAMA Intern Med. 2015;175(4):542–548. doi:10.1001/jamainternmed.2014.8187

• Cold immersion and noradrenaline. Šrámek P, Šimečková M, Janský L, et al. “Human physiological responses to immersion into water of different temperatures.” Eur J Appl Physiol. 2000;81(5):436–442. doi:10.1007/s004210050065

• Creatine and cognition. Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. “Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials.” Exp Gerontol. 2018;108:166–173. doi:10.1016/j.exger.2018.04.013 — and Prokopidis K, et al. Nutr Rev. 2023;81(4):416–427 (effect strongest in older adults).

• Metformin blunting exercise adaptation. Konopka AR, Laurin JL, Schoenberg HM, et al. “Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.” Aging Cell. 2019;18(1):e12880. doi:10.1111/acel.12880 — and Walton RG, et al. (MASTERS trial), Aging Cell. 2019;18:e13039.

• Psilocybin and depression. Goodwin GM, Aaronson ST, Alvarez O, et al. “Single-dose psilocybin for a treatment-resistant episode of major depression.” N Engl J Med. 2022;387(18):1637–1648. doi:10.1056/NEJMoa2206443 — and Carhart-Harris R, et al. N Engl J Med. 2021;384(15):1402–1411.

If this gave you something to think about, pass it on. Restack it for someone who’d argue with you, reply and tell me where you land, or subscribe if you’re new here. I read everything.

In Search Of is where I chase the questions the wellness industry is too sure about.

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WHO I TALKED TO

Simon came to longevity sideways. He was running a sleep startup when someone dragged him to a talk by people who said, out loud, that they wanted to cure aging. He thought they were crazy. Then he sat through it. “This completely changes how I think about everything,” is how he describes walking out.

The second time his thinking flipped was about skin. He started working with a scientist named Francois, two decades in longevity molecule discovery and more than a decade in cosmetics, who had led innovation and longevity research at a European cosmetics company doing around 700 million dollars. Simon built a whole-body longevity platform called Jung+, added a skin formula almost as a side quest, and is now building a skin-longevity supplement company. The science, in his words, blew his mind the way longevity itself first did.

I have heard a lot of founders say their mind was blown. I went anyway, because the thing he kept circling is one I think the whole industry has wrong.

THE 500 DALTON PROBLEM

Here is the pearl Simon handed me, and it is the one to keep.

There is a rule in dermatology called the 500 Dalton rule. A Dalton is a unit of molecular size. For a topical ingredient to cross the skin barrier, it has to be smaller than roughly 500 Daltons. The epidermis is, in Simon’s framing, a wall. Hundreds of millions of years of evolution engineered it to keep things out. Above 500 Daltons, the molecule mostly does not get through.

Now look at what the anti-aging shelf is actually selling you. Hyaluronic acid, the molecule everyone wants for plumpness, runs in the tens of thousands of Daltons and often far higher. Topical collagen and copper peptides are large too. The aging machinery they are supposed to reach, collagen, fibroblasts, the dermis, all of it sits below the wall. The molecules that are supposed to fix it cannot get down there.

“The difference between the mechanistic reality and what the skincare industry is selling is absurd,” he said. Hyaluronic acid sitting on top of your skin can give you surface hydration. Surface hydration is not aging. The organ needs hyaluronic acid inside it to bind water. Painting it on the wall does not put it in the room.

I want to be fair to the shelf, and so was he. Some topicals genuinely work. Retinol changes the biological age of skin, full stop. Microneedling improves delivery. “Many of them are crap,” he said of in-clinic treatments, “but some of them do actually alter biological aging.” The point is not that topical is useless. The point is that the dominant format is sold as if it reaches a place it physically cannot.

“YOU NEED TO SWALLOW YOUR SKINCARE”

That was my reframe back to him, and he took it. If the wall keeps things out, you feed the organ from the bloodstream instead. Ingest it, let it reach every organ system, skin included.

The feedback he describes from the supplement they built is the kind founders inflate, and he knows it. “This isn’t founder bullshit,” he said, before telling me the one that made me laugh. A customer’s podiatrist, of all people, told her that her feet were looking younger. Feet. The part of you nobody is putting serum on. If something is showing up on the skin you ignore, the signal is coming from inside.

Hold this loosely. These are anecdotes, not a trial. Glow is not a biomarker. The honest version of the inside-out thesis is that the mechanism is sound, systemic delivery reaches tissue that a cream cannot, and the human evidence for swallowing your way to better skin is still thin and mostly funded by the people selling the capsules. Simon’s own framing is the right one anyway: skin is a whole-body output. “The skincare industry has been trying to sell people a really narrow format that can maybe move five percent of the needle,” he said. Sleep, nutrition, exercise, the actual drivers, never made it into the bottle.

TWO ROOMS THAT DON’T TALK

So why is skin longevity behind body longevity by years, when it is the most visible aging any of us experience?

His word for the whole category is toddler. “Skin longevity feels like a toddler learning to walk.” Three to five years behind the rest of longevity, by his count, and saddled with a problem the rest of longevity does not have. The beauty industry is a behemoth. It has speed, money, and enormous momentum, a giant ship already pointed in one direction. Longevity asks it to turn the whole ship. Ships that size do not turn because the science changed.

THE TELL: A LONGEVITY MOLECULE IN A DAY CREAM

If you want proof the science is being bent toward the customer instead of the other way around, follow the smartest money.

In 2024, L’Oréal and Nestlé put roughly 66 million dollars into Timeline, the Swiss biotech behind Mitopure, a purified form of urolithin A spun out of EPFL. Urolithin A has real cellular data behind it, mitophagy, mitochondrial cleanup, the kind of mechanism longevity people take seriously. Timeline started in muscle. Then it went to skin. And L’Oréal is now routing that molecule into a Lancome longevity skincare range. Into creams.

Simon is careful here, and so am I. He is not on Timeline’s science team and neither of us knows where their topical-versus-oral efficacy conversation actually lands. There may be real reasons to go topical. There are serious people doing serious research inside these companies.

But the format choice tells you who the science is serving. “There’s no way they didn’t make this decision partly because beauty customers buy cream,” he said. The molecule bends to the shelf the customer already shops. That is the ship turning the science, not the science turning the ship.

THE NUTRAFOL PLAYBOOK

So what does skin longevity look like when it finally walks?

Simon’s analog is Nutrafol. Before Nutrafol, thinning hair meant topical minoxidil and serums and shampoo. Nutrafol asked a different question, what is happening with your internal nutrition, and built the hair wellness category around the answer. One SKU at first. Then a line. Unilever bought it. It has since expanded into skin. “A company that made people rethink a part of their body through supplements,” is how he put it.

BUILDING THE GROUND TO STAND ON

A toddler needs solid ground before it can walk, and the ground under skin longevity barely exists. There are no agreed biomarkers. The hallmarks of skin aging are still being written. Three different people Simon knows are each building a different skin-aging clock, which tells you we cannot yet agree on what we are even measuring.

So he is building the ground himself, as a whatsapp group chat (you can apply to join Skin Longevity Pro here). Dermatologists and plastic surgeons who actually see patients. Longevity physicians. Functional doctors. Scientists, who see all of it differently than the doctors do. Founders and formulators. People building skin-aging clocks. And, the addition I liked most, a lawyer who works on claim substantiation in skincare, in the room while the science is being argued, so someone can say what any of it is actually allowed to mean.

He is building a product into that gap too. It is in stealth, in vitro trials just starting, a first white paper done. I am leaving the details where he left them, because he asked, and because a founder going to in vitro is not the same as a founder going to market.

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WHERE THIS LEAVES US

Skin should have been the easy win for longevity. It is the most visible organ, the one we are vain about for an entire lifetime, the one with the biggest, richest industry already built around it. Instead it is the toddler. Behind body longevity, because the people who understand how skin ages and the people who sell you skin live in separate rooms, and the bigger room keeps winning the argument by sheer momentum.

The 500 Dalton rule is the whole thing in one number. Most of what we rub on our faces cannot reach the part that is aging. We have known this since 2000. We sell against it anyway, because the cream is the format the customer was taught to buy.

Whoever builds the hallway between those two rooms, shared biomarkers, an inside-out category that does not just rebuild the nine-step shelf in pill form, a table where the scientist and the dermatologist and the claims lawyer argue in front of each other, gets to define what skin longevity even means. Right now that hallway is a group chat. I’ll take the group chat. It is more than the behemoth has built.

I keep mapping longevity to find the places it has been built for real. Skin is still not one of them. But for the first time it looks like someone is laying the floor.

Appendix: what informed this piece

Bos, J.D. and Meinardi, M.M.H.M. (2000). The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Experimental Dermatology. (The penetration threshold the whole piece turns on. DOI: 10.1034/j.1600-0625.2000.009003165.x)

Jin, S. et al. (2023). Hallmarks of Skin Aging: Update. Aging and Disease. (Seven molecular hallmarks of skin aging. DOI: 10.14336/AD.2023.0321)

Kream, E. et al. (2025). Skinspan: A Holistic Roadmap for Extending Skin Longevity With Evidence-Based Interventions. Journal of Cosmetic Dermatology. (Ranks interventions by evidence strength. First-line: sun protection, topical retinoids, antioxidants, which is why retinol earns its place above.)

(2025). Longevity cosmeceuticals as the next frontier in cosmetic innovation: a scientific framework for substantiating product claims. Frontiers in Aging, vol. 6. (On why skin biomarkers and claim substantiation are still unsettled, the exact gap Simon’s group chat is poking at.)

Timeline / Amazentis Series D coverage (2024). L’Oréal and Nestlé invest CHF 56M ($66M) in the maker of Mitopure (urolithin A); Lancome longevity skincare range follows. NutraIngredients; Timeline; Beauty Independent. (Urolithin A’s cellular and muscle data are the strongest part; the human topical-skin efficacy story is the newest and thinnest part. Worth holding loosely.)

Nutrafol / Nutraceutical Wellness, acquired by Unilever (2022). Built the hair wellness nutraceutical category from inside-out nutrition; expanded into a Clear Skin nutraceutical in 2024. Unilever. (The category-creation template Simon points at.)

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In Search Of is where I chase the questions the wellness industry is too sure about.

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This is the House Call I promised.

SERVICE TESTED: SMILE HOUSE

55 Warren Street, Tribeca, NYC | smilehouse.co

THE SETUP

I have hated the dentist my whole life. I said as much within a minute of walking in. I’m a prime client. Terrified, and here anyway.

So I walked into 55 Warren Street already suspicious. It looks like a boutique hotel, and a beautiful room is a very effective way to distract you from mediocre care. Cody, who runs the place with his brother Julian, described it the way you’d describe a room and not the way you’d sell one: “designed to feel more like a living room or boutique hotel.” Then the reasoning. “Dentistry is often associated with fear, stress, anxiety, needles, pain. Here it’s about nervous system regulating.” A dental office organized around the nervous system is either a marketing line or the most current thing in the building. (I’ve been writing about nervous system regulation as the 2026 throughline for a while. I did not expect to run into it at the dentist.)

Then he handed me a saliva test before he handed me a chair. That is when I understood what kind of place this was.

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WHO BUILT IT

Smile House is the downtown expansion of Dr. Jonathan B. Levine’s practice, JBL New York City, which has run on Fifth Avenue for close to 40 years. “He’s got 27 patents on teeth whitening and therapeutic products,” Cody told me. If you’ve ever used one of those blue-light whitening devices, you’ve used his father’s work. That’s GLO Science. Cody and his brother Julian grew up inside the business. “I was seven, my brother was ten, and we started packing our first product on the ping pong table.”

Cody brought the practice downtown. Fourteen doctors across every specialty under one roof, seven suites, multi-specialty on purpose. “You’re not getting sent all over town and things are getting lost in translation.”

The credibility, for me, is in the origin. The GLO Good Foundation, co-founded in 2011 by Dr. Levine with his wife Stacey, Cody, Julian, and longtime friend Lenny Kravitz, started with a woman in Rwanda. The way Cody tells it, she “lost her four front teeth during the genocide in ‘94, by the butt end of a machete,” and when they rebuilt her smile, “that was the first time she looked in the mirror in 18 years.” His verdict on the moment was “pretty cool,” which is characteristically not what it was. Ten years of free missions in the Bahamas followed, with more coming in the States.

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WHAT ACTUALLY HAPPENS THERE

Cody walked me through the diagnostic framework. They call it mouth mapping: “a 360 degree view of your mouth as it relates to whole body health,” turned into “a personalized, data-driven plan.” Four pillars. Aesthetics is full smile design, with a digital render of your future smile before anyone touches a tooth. Structure is airway and jawbone, which is how a sleep and breathing evaluation ends up happening at the dentist instead of three referrals away. Function is how the teeth meet and chew. Biology is what is actually living in your mouth, and what it might be saying about the rest of you.

The saliva work runs two levels. The point-of-care test, “15 minutes, we get results,” flags urgent bacteria on the spot. Then the lab version: “we’re testing 250 biomarkers,” back in about two weeks, a full read on the oral microbiome. Cody’s framing: “like your blood work, this is a salivary test. Early indication of downstream impact on cardiac health, cognitive health, you name it.” That is a big claim, and I want my own results before I co-sign the whole chain. But it is the first time I have left a dental chair curious about a result instead of relieved it was over.

I covered the science underneath all this in last week’s map, so I won’t relitigate it here. The part worth naming is the part almost nobody in this category reaches: the loop closes. Most diagnostics hand you a number and a shrug. I’ve watched company after company do exactly that, call it empowerment, and move on. Cody named the gap as well. “We’re all optimizing. Thank you for the data, what do I do now? We connect the dots and provide those treatments.” That is the entire difference. Smile House is one of the only places I’ve seen building clinical infrastructure around the science rather than citing it in a brochure. “Root cause analysis is really our main focus.”

EVERYTHING ELSE ON SITE

The range is a lot, in the good way. A CBCT scanner, “a three dimensional CAT scan, nose to throat,” for sleep and airway: deviated septums, a constricted throat, the mechanical reasons people snore and wake up at 3 a.m. It also reads below the gum line for hidden infection and the leftovers of old dental work. “We see a lot of that,” Cody said. “Unfortunately.” The in-house lab makes crowns, bridges, veneers, and full-mouth reconstruction, designed digitally and sometimes turned around in a day. The finishing hand belongs to Fatty, their master ceramist from Italy. “Think master somm in the wine space, but a true artist.” TMJ care runs from 30-minute jaw massages to Botox to M-Face, a non-invasive high-frequency muscle stimulation device. Estheticians twice a week. Implants, bone grafts, gum grafts, surgery, all handled in-house.

I also had stitches removed while I was there, left over from a procedure in another city. My healthcare, like most people’s, is scattered across wherever I happened to be when something needed attention. Smile House absorbed it without fuss. That flexibility is rarer than it should be.

I left with oral probiotics (not standard dental inventory), the family’s toothpaste, and floss I am genuinely using. Cody calls one of the products his “killer product,” expensive to make, “like an ice bath for your mouth.” He would not say which one. Same thinking as the practice: the mouth as an ecosystem, not a set of teeth to be cleaned.

WHY THIS ONE MATTERS

It’s one location. It’s high-end. Not everyone will have access to this, and that is worth saying out loud.

The map showed the category in pieces. Consumer brands with nothing diagnostic underneath. Biological dentists with the right science and the wrong brand register. Microbiome tests with no clinician to read them back to you. The version where your microbiome gets sampled the same day your teeth get cleaned, where someone reads your saliva next to your blood, where your daily products are calibrated to what your mouth actually needs, mostly does not exist yet.

Smile House has built most of it. A category needs a working example before anyone can fund or build the version that scales. This is the working example, and that is the reason it matters past the four walls of one Tribeca practice.

Cody’s whole philosophy is that diagnostics come first. I’m still waiting on my 250 biomarkers to tell me whether my mouth has been trying to explain my gut to me this entire time. I’ll report back.

TL;DR

The Seal Pillar

Verdict

Did it deliver?

Yes. Left with data incoming, products I actually use, and a rebooked appointment.

Science or snake oil?

The 250-biomarker saliva test is the most interesting thing I’ve walked out of a dental office holding. The clinical infrastructure under it is the part missing from most longevity-dental talk.

Pain, price & weirdness

Premium, one location only, not for everyone, and worth saying so. The anxiety, though, solved by design.

Would I do it again?

Yes. And I want to. Which, from me, is the entire endorsement.

The Seal: [5/5]

Further reading

The Most Under-Diagnosed Organ in Longevity - the map, the science, and the integration layer no one has built yet. Full citations live there.

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If this gave you something to think about, pass it on. Restack it for someone who’d argue with you, reply and tell me where you land, or subscribe if you’re new here. I read everything.

In Search Of is where I chase the questions the wellness industry is too sure about.

Energy: What Is It, Really?

The most-used word in wellness might also be the least understood.

We chase it, sell it, build entire industries on it, and almost no one can tell you what it actually means.

I have spent my life inside both definitions, and for most of that time I kept them in separate rooms.

Two rooms, one word

Acupuncture was normal in my house before I knew it was controversial anywhere else. My mother talked about energy healing the way other mothers talked about vitamins, and there was a whole Eastern European and Eastern-medicine lineage behind her, the kind of inherited knowledge that doesn’t ask permission from a journal. Years later I got Reiki certified myself. I have felt something on those tables. Whether it was real or whether it was in my head I genuinely cannot tell you, and I’ve made a kind of peace with not knowing.

Then I spent the rest of my life in the other room. The hyperscience one. Biomarkers, bloodwork, the quantified everything. For years the two rooms had no door between them. Energy-the-mystical on one side, energy-the-measurable on the other. Same word, two religions, no diplomatic relations.

What actually did

A paper by Martin Picard reopened the border. Picard runs a mitochondrial psychobiology lab at Columbia, and his model does something quietly radical. It takes the most woo-adjacent word in wellness and gives it a hard mechanism. His Energetic Model of Allostatic Load argues that chronic stress carries a literal metabolic cost, and that aging happens partly because the body runs an energy budget like any household.

We have spent a decade measuring the body as a pile of biological readouts, this marker, that level, the number on the ring. Picard points somewhere else.

That’s not a tweak, it’s a different lens on the whole thing. And it sent me back to the other room, the one with my mother in it.

The danger zone keeps becoming the standard of care

The smug position is that Picard’s energy is real and my mother’s energy is nonsense. I held that position for years. I’m less sure now, and not because I’ve gone soft. I’m less sure because I’ve watched the danger zone become the standard of care more than once.

👉 Acupuncture is the cleanest example. For years you could only find it in a basement, from the one practitioner someone’s aunt swore by. It looked exactly like the thing a sensible person dismisses. Except acupuncture has real schools, four and five years of training, a body of practice older than every institution currently dismissing it. Argue with the theory of meridians and qi all you want, and I’ll argue alongside you. But “I don’t understand the mechanism” was never the same sentence as “there is no effect.”

👉 Meditation made the identical journey inside my lifetime, from Eastern fringe to the thing your cardiologist now recommends with a straight face.

This is where the rigor crowd gets sloppy.

Sometimes there’s no science because the science is hard. Sometimes there’s no science because nobody bothered to look.

The gap between them is exactly where thousands of years of Eastern and ancient medicine has been sitting, waiting. Ayurveda. Saunas. Cold. Chinese herbs. It is genuinely hard to look at practices that survived across millennia and whole civilizations and conclude they’re all placebo. Persistence isn’t proof. But it isn’t nothing.

The grift problem, which is real

The same unmeasurability that protects ancient practice from dismissal also protects every charlatan with a certificate from a thirty-minute online course. Energy is hard to measure. So is the quality of the person selling it to you.

Supplements spent decades in exactly this spot, a few real products floating in an ocean of garbage, until the category started to grow up. The SuppCo and Function-style consolidation is the tell: third-party testing, real data, the beginnings of a framework for telling good from bad. That’s the part energy is still missing. The absence of a measuring stick doesn’t make a field worthless. It makes it unpoliced. And unpoliced is a stage, not a verdict.

So I’ve built a layman’s test, and it’s embarrassingly simple: has this been around a lot longer than I’ve been alive? Not as proof, as a filter. Things that persist for thousands of years are, at minimum, usually not acutely dangerous and usually not a fad. It’s a low bar. But it sorts the 5,000-year-old practice from the post-COVID manifestation content flooding everyone’s feed, and most days that’s a useful sort.

The edge of the map

Then there’s the territory where I genuinely don’t know what I’m looking at.

A doctor told me recently that we might eventually move toward frequency and sound as forms of healing, which is the kind of sentence that lands you squarely in quantum-flavored territory, and I want to be careful, because this is where credibility goes to die. But. There was a study in Mexico City that used light, specifically a light-activated compound, to clear HPV and precancerous cervical lesions in a small group of women. That’s photodynamic therapy. It’s real, and while it’s light plus a drug rather than light alone, it points at something: light doing biological work. There’s early preclinical work out of MD Anderson probing whether biofield therapy affects pancreatic cancer cells in a dish and in mice.

I am not telling you energy healing cures cancer.

I’m telling you serious institutions are starting to point instruments at questions they wouldn’t have touched ten years ago, and I’m old enough to have watched what happens to the things we’re certain are nonsense, right up until they aren’t.

Back to the two rooms

Which brings me to my mother, and to a word that means the fuel in my cells and the thing she said she could feel moving through her hands. Maybe they never meet. Maybe Picard’s energy and my mother’s energy are two unrelated things wearing the same name, a coincidence of language. Or maybe the reason the word survived in both rooms for so long is that some part of us always knew they were pointing at the same thing, and we’re only now building the instruments to find out.

What is energy, really? I don’t know yet. But I’ve stopped being embarrassed by the question.

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If this gave you something to think about, pass it on. Restack it for someone who’d argue with you, reply and tell me where you land, or subscribe if you’re new here. I read everything.

In Search Of is where I chase the questions the wellness industry is too sure about.

I have wholeheartedly hated the dentist my whole life.

I am, by most measures, pain-tolerant. But put me in a reclining chair under a fluorescent light with a stranger holding a vibrating tool an inch from my molars and I become a person I don’t recognize. The fear is older than I can trace. It has never softened.

So for most of my adult life, I sorted dentistry into a mental category I called classic healthcare — the kind of thing you do when something hurts. I treated my mouth the way most people treat an MRI: necessary occasionally, unpleasant always, and unrelated to the proactive work I actually invested in.

That assumption has, quietly, started to look very wrong.

The science that changed how I think about my mouth

In 2019, a paper in Science Advances did something most dental research never does: it crossed disciplines. Researchers led by Stephen Dominy detected Porphyromonas gingivalis (a common gum-disease bacterium) in the brain tissue of Alzheimer’s patients. Not the saliva. The brain.

The implication was uncomfortable: an oral bacterium might not just correlate with neurodegeneration. It might cause it. The follow-up drug failed its trial in 2021 and the mechanism is still debated - but the underlying observation, that oral bacteria don’t stay in the mouth, has held up.

A few things to anchor on:

• 6.87x higher risk of Alzheimer’s dementia for severe periodontitis (2025 meta-analysis, Journal of Evidence-Based Dental Practice, 24 studies)

• Periodontitis is now an independent cardiovascular risk factor in multiple major reviews

• You swallow ~600 times a day. The oral microbiome is upstream of the gut — every swallow inoculates it

I didn’t arrive here through dentistry. I arrived through gut. When I was doing longevity reviews in Paris, the team at ZOEI walked me through research connecting oral microbiome composition to brain aging. In the practitioner circles I move in, this has crossed from “fringe” to “emerging biomarker” in the last 18 months.

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The category is being built in fragments

I spent the last few weeks mapping who’s actually building here. The full map went up on LinkedIn (embedded below). The short version:

🏛 Longevity Dental Clinics: three credible US operators

• Smile House (Tribeca) - Dr. Jonathan Levine + sons. 250-biomarker saliva test, Mouth Mapping framework

• Rejuvenation Dentistry 0 Dr. Gerry Curatola, NYU professor, forty years deep

• SAMA Oral Health - Dr. Jaskaren Randhawa, membership model with microbiome testing built in

🛋 Modern Dental Experience: Tend, Quip. Got the front of house right. Didn’t go upstream into biology. A better waiting room isn’t a different paradigm.

🧬 Functional / Biological Dentists: Dr. Mark Burhenne, Dr. Steven Lin, Bruno Integrative. Right science, wrong brand register. Correct for a decade, still looking like alternative health from 2014. The category needs what Equinox did for the gym.

🔬 At-Home Microbiome Testing: Bristle (800+ species, mail-in), Oral Genome (chairside, 15 min), Viome, Oralis 1

🧴 Premium consumer brands are having their skincare-circa-2017 moment, making the daily stuff good enough to actually use. People will tell you the pretty tongue scrapers are just branding. I don’t buy it. A treadmill was a treadmill before Equinox put a brand and a room around it, and that is what got people on it five times a week. Design is not the opposite of substance. It is how substance gets used.

• Boka (nano-hydroxyapatite, 320% YoY growth), RiseWell, Davids, Twice, Lumineux, Agent Nateur, Marvis (the heritage benchmark)

• Ancient Practice, Modern Packaging: tongue scraping and oil pulling, 5,000-year-old Ayurvedic rituals now rebranded as “microbiome support.” Which is exactly what they always were: Cosmic Dealer, Surya, Terra & Co.

🧠 AI Diagnostics: Pearl, Overjet, VideaHealth. The radiograph-reading layer that makes the rest of the stack affordable at scale.

⚙️ Infrastructure: Torch Dental (the Boukadoum brothers), digitizing the $20B+ dental supply chain. The clinic of the future can’t exist on an analog back-end.

What the comments surfaced

The map went up Tuesday and the comments did something better than agree - they extended it. Two sub-categories I’d underweighted, all shown to me by people building and practicing in the space:

Oral microbiome therapeutics: engineering the bacteria, not just testing or cleaning:

• Primal Health (Dr. Emily Stein): patented, NIH-funded science shifting bacteria from sugar- to protein-metabolizing

• Ostia Sciences (Dr. Michael Glogauer, UofT): a Phase 2 probiotic lozenge for gingivitis

• FoodBIOME (Guy Lopez): a functional-food platform engineered to feed beneficial bacteria

• MyFitStrip + Per Os Biosciences: a prebiotic gum shifting the mouth toward nitric-oxide-producing bacteria

Chairside biomarker testing: same-visit diagnostics between the mail-in test and the clinic:

• Drül: nucleic-acid saliva testing, results in ~30 minutes

• ARKRAY’s SillHa; seven biomarkers in five minutes, already in practices

The pattern underneath both: the consumer brands at the top of the stack are only as good as the therapeutics and diagnostics underneath them. The thesis applies a layer deeper than the original map gave it credit for.

And the most valuable part wasn’t the map - it was who it brought in. I had the pleasure of connecting with Dr. Megan Pugach-Gordon and Dr. Jill Sirko, both out of the ADA Forsyth Institute (formed when the Forsyth Institute joined the American Dental Association’s research arm). Megan’s work sits right at the enamel-microbiome-saliva interface, including using beneficial bacteria to prevent tooth decay. The two of them are building something together in this space - exactly the kind of science-first work the category needs more of.

What’s actually missing

What no one has built - and what investors should be looking for - is the layer that integrates all of this into something a consumer can actually use.

The dream version is mundane, but:

• Your microbiome is sampled the same day your teeth are cleaned

• Your dentist functions as a longevity practitioner, reading saliva alongside blood

• Your daily products are calibrated to what your microbiome needs, not what a brand is selling

• The data goes somewhere useful

That workflow doesn’t exist yet. The data exists. The clinicians, the brands, the diagnostics, the infrastructure - all exist. What’s missing is the connective tissue that turns disconnected purchases into one coherent picture.

And the mouth is just one example of a pattern repeating across consumer longevity: a category emerges in fragments, the science outpaces the infrastructure, and consumers end up with another biomarker, another test, another product, and no way to integrate any of it.

We are not short on data. We are short on the layer that makes it usable. The next decade of longevity isn’t about generating more measurements. It’s about helping people navigate the ones they already have.

What I’m actually doing

• 💧 Water flosser: won’t travel without it

• 🪥 Tongue scraper every morning (Cosmic Dealer; Surya is the accessible US option)

• 🌿 Oil pulling with Terra & Co., when I remember

• 🧪 Saliva microbiome test: results pending. I’ll write about what comes back.

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Next Thursday’s House Call goes deep with Cody Levine at Smile House — the closest thing I’ve found to the full-stack longevity dental practice this category needs. Subscribe if you want to read it.

Disclaimer: This is one person’s reading of an emerging and unsettled area, not medical advice. Talk to someone who knows your own history before changing anything.

At a recent dinner on longevity, after the usual macro trends and clinic talk, the question landed where it always lands.

What supplements are you taking?

The answer worth giving is the same one worth giving every time the question comes up.

For what?

Three things happened over the past few weeks that mean the question is finally about to matter.

Three moves. One outcome.

1. Function Health acquired SuppCo (May 12, 2026).

SuppCo is the independent supplement verification platform that anonymously buys products off brand websites, ships them to ISO 17025 accredited labs, and posts the results, pass or fail, on a public product page.

• TrustScore rates more than 35,000 products on a 10-point scale across 30-plus quality attributes.

• In one round of testing, four of six popular creatine gummies on Amazon contained essentially no creatine. Two contained none at all. The failing products had sold more than 50,000 units on Amazon the month before.

• Across SuppCo’s broader testing, roughly six in ten products fail basic identity and potency.

That platform now sits inside Function Health, which already runs diagnostic panels for hundreds of thousands of people (and i’m proud to be an early investor in). The watchdog nobody was paying for is now baked into the place people actually look at their numbers!!

2. H.R. 8370, the Dietary Supplement Listing Act of 2026 (introduced April 20).

Rep. Maxine Dexter’s bill would create the first mandatory FDA listing regime for supplements.

• Every supplement marketed in the U.S. has to register with the FDA.

• Within 2 years, the agency builds a public, searchable database of every product, every ingredient, every claim.

• Existing products get 18 months to list. Labels eventually carry a listing number.

• The bill explicitly does not require pre-market approval, which is exactly why it has a real shot at passing.

3. FDA finalized its updated General Wellness guidance (January 6, 2026).

Wearables that measure blood pressure, glucose, HRV, blood oxygen can now sit in the wellness lane if they do not claim clinical equivalence. WHOOP got a warning letter in July 2025 for crossing that line. The rules are clearer now.

The boring true thing about blends

Most supplement blends cannot fit clinical doses of their headline ingredients into one capsule. The peer-reviewed sports medicine literature has been pointing this out for years (Burke et al. in Sports Medicine, on the dosing problem in multi-ingredient performance products). Even when an ingredient is well-studied at, say, three grams a day, the blend gives you two hundred milligrams of it on a base that may or may not disintegrate properly in the gut.

The brand is real. The dosing.. that’s another story.

This is the question the TrustScore is about to make legible to a normal consumer for the first time: not “is this product good,” but “does this product deliver what it says, at the dose the studies actually used?”

What supplement partnerships are actually solving

Inside any operator with a member base, gym, clinic, hotel, beauty platform, supplement deals usually solve one of three things:

• A revenue line

• A retention story

• A perceived science gap in the offer

Almost none of them are solving a deficiency. Almost none of them are clinically dosed. The brands that get through a serious procurement filter, that is, the ones that survive on safety, dosing, and supply chain rather than margin, are a small subset of what the consumer sees at retail.

A 1:1 personalized service model breaks the minute the front desk becomes an upsell counter. That is the same structural problem the consumer faces in their own bathroom. The verification layer being built now collapses that asymmetry: the front-desk pitch and the lab report finally live in the same place.

What survives a verification layer

Mono-ingredients with real supply chain authority.

• Vitamin D

• Magnesium(s)

• Creatine monohydrate (ironically, given the gummy story above) etc.

• Thorne is the canonical example of a brand built to survive this kind of scrutiny: NSF-certified facility, 40+ NSF Certified for Sport products tested against 270+ banned substances, minimum four rounds of testing per product. That stack is defensible on paper. The TrustScore will reflect it.

Longevity-specific blends only when the trial work is actually there.

NOVOS Core is one of the few longevity-branded products with a registered human trial. Their randomized, double-blind, placebo-controlled trial out of the University of Surrey (ClinicalTrials.gov NCT06145087) showed:

• +3.4% improvement in endothelial function (FMD)

• −8.5 mmHg in systolic blood pressure over six months

The endothelial number is in the range of what sustained HIIT produces in published exercise studies. That is an uncommon result for a multi-ingredient supplement, which is precisely why it is worth pointing at.

What does not survive.

The rest of the longevity supplement aisle, the lifestyle blends, the celebrity-doctor-fronted stacks, the twenty-pill subscription “core” routines, are about to face the database, the TrustScore, and a consumer who can finally see the math.

What this means for the bathroom counter

It gets smaller, more boring, and more honest.

• Legacy brands with real supply chain moats survive at scale.

• The knock-offs get cleaned up.

• Longevity supplements grow, but as a thin fringe on top of a defensible core stack, not as the whole stack.

The category levels up overall. That is good for the consumer. It is good for the science. It is bad for anyone who has been pricing branding into a capsule.

Back to the dinner question. The right one is still for what.

• Are you deficient and your blood shows it?

• Are you trying to sleep better, recover faster, hit a specific number?

Start there. Take the data. Then look at the product.

Now, for the first time, the data and the product finally meet in the same app.

Stop paying for expensive pee.

CTA

What is actually in the bottle on your counter? Take a photo, look it up, see what the TrustScore says. If something on the shelf surprises you, tell me. The group chat that swears by their twelve-pill stack probably needs this one more than you do.

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References

• Function Acquires SuppCo to Bring Trust and Clarity to Supplements. PR Newswire, May 12, 2026. https://www.prnewswire.com/news-releases/function-acquires-suppco-to-bring-trust-and-clarity-to-supplements-302769718.html

• SuppCo. Creatine Reality Check: The Failures We Found When Testing Popular Products (lab analysis, four of six gummies failed). https://supp.co/articles/suppco-tested-creatine-testing-results-gummies-failed-lab-analysis

• SuppCo. Product TrustScore methodology (10-point scale, 30+ quality attributes, 35k+ products). https://supp.co/trustscore/about/product-trustscore

• H.R. 8370 - Dietary Supplement Listing Act of 2026, 119th Congress, introduced April 20, 2026. https://www.congress.gov/bill/119th-congress/house-bill/8370/text

• FDA. General Wellness: Policy for Low Risk Devices, final guidance, January 6, 2026. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-wellness-policy-low-risk-devices

• Burke, L.M., et al. (2017, with subsequent updates). Practical Issues in Evidence-Based Use of Performance Supplements. Sports Medicine, 47(Suppl 1). https://link.springer.com/article/10.1007/s40279-017-0687-1

• NOVOS Core Clinical Trial Reveals Cardiovascular Benefits in Aging Adults. PR Newswire; trial registered as NCT06145087, University of Surrey. https://novoslabs.com/blog/supplements/novos-core-clinical-trial-results-longevity-supplement/

• Thorne. Unparalleled Quality (NSF Certified for Sport program, 270+ banned substances tested). https://www.thorne.com/quality

• Crawford, C., et al. (2024). Label Accuracy and Quality of Select Weight-Loss Dietary Supplements. PubMed: 39770990. https://pubmed.ncbi.nlm.nih.gov/39770990/

I got my first acupuncture needles at nine. My mom said it was important to help with stress from school. I didn’t push back.

I’m telling you this because it’s the framing I gave the room at Wellist Week in Miami and it’s the framing I keep coming back to: nothing has changed in 3000 years, and yet everything is changing.

With Tino de Martino and Greg Scheinman

A city making a claim

Wellist was the first edition of a new global forum for the business of wellness, built by Myk Likhov and Alhia Chacoff-Berger, anchored by the Miami Design District, and co-signed by the city itself. Mayor of Miami Beach Steven Meiner opened the week. Mayor of Miami Eileen Higgins closed parts of it.

The whole thing read less like a conference and more like a city making a claim. And it did the job: 680 registrants, 70 curators, 92 speakers, 53 satellite events.

It was a city overtake, one that I envision becoming the new Art Basel at scale. And i’m here for it!

I went as both speaker and reporter. I am still processing what I think, but here is off the cuff recap.

What hasn’t changed

We have been doing most of this for three thousand years. The Greeks. The Romans. My family in Poland.

Sauna, cold, fasting, breath, sleep, walking, time outside, time with people. Everything we now sell with a clinical asterisk and a recurring revenue model has been, somewhere, somebody’s grandmother.

The Swami who spoke on Day One - Chidananda, a former investment banker turned Vedic monk, which is its own incredible American story - said the quiet part out loud: the fear of death is the hidden driver behind most of the desire to live longer, and spirituality is the only thing that meaningfully resolves it.

I don’t think you have to be religious to take the point. The point is that the wisdom layer is older than the data layer, and we keep rediscovering it under new branding.

Myk Likhov and Alhia Chacoff-Berger, founders of Wellist, at the Opening Party

What’s changing

Health left the doctor’s office. That is the actual shift.

At the conference, McKinsey said that 84% of consumers globally list wellness is a top priority. They also stated that only thirteen percent of these same consumers say they are achieving their goals. Funny aside: Eric Farlardeau from MckInsey who presented at the conference and I worked on Equinox’s strategy together years ago, when “longevity” still made every brand nervous.

Almost 20% of americans have already tried GLP-1s. That is a behavioral statistic dressed in clinical language, and it tells you the consumer has stopped waiting for permission. And if you want to read more on consumer agency (a topic I think is the KEY driver of this industry), I couldn’t recommend David Shaywitz thinking more!

AI is the unlock

This was in every single conversation whether the panel was about it or not.

And I can’t argue this more: AI is the unlock. Not because it diagnoses better than your doctor (it sometimes does, and sometimes doesn’t), but because it solves a problem the wellness industry has had since the first multivitamin: personalization at scale was a contradiction in terms.

You either had a $40,000-a-year concierge program (I helped build one of those ;)) or you had a generic supplement aisle. There was no middle. AI collapses the middle.

That is the actual story underneath every “AI in wellness” panel - and it’s why even Soho House, which is in the relationship business, is now investing in an AI-powered chatbot to help members navigate amenities across properties.

Tino De Martino, Soho House’s Head of Wellness for North America, told me and Greg Scheinman this during our panel: membership is a relationship, not an access pass, and AI is what lets you scale the relationship without diluting it.

A brand for everyone is a brand for no one

Tino and I spent most of our time on stage debating how you build a brand and a community in a market that has become, frankly, commoditized.

My provocation, which I will say again (and I did pick it up from Equinox’s Chairman), here because I believe it: a brand for everyone is a brand for no one.

Equinox’s President - Marc - and Eileen Higgins - Mayor of the city of Miami - discussing what makes Equinox special!

The capital is here, and it’s sorting

The investment room had the most institutionally credentialed lineup I have seen at a wellness event from L Catterton (LVMH-backed) to Goldman Sachs alums.

The bar has moved from post-revenue to post-profit. They are screening for measurable outcomes, clinical credibility, and founders who can command their numbers without a deck.

The Future Laboratory’s Madeleine Boyd called this “the Age of Proof.” She also pointed out that 57% of US and UK early adopters now think “longevity” has become an overused marketing term, rising to 64% among Gen Z. I’d argue we crossed that threshold a year ago. The market is just catching up to its own fatigue.

The Age of Proof, embodied

Speaking of the Age of Proof - I had a long dinner with Chris Mirabile, founder of Novos. More to come on what he’s building, but the headline for this piece is simpler: Novos Core has a study showing it actually works, and Unilever just put capital behind the company.

There is a particular pleasure in watching someone you connected with years ago (and use the product), when the category was still mostly vibes and TED talks, grow up into the version of the company they always said they were going to be. Chris was disciplined about the science when discipline was unfashionable. Now the discipline is the moat. The clinical data is the product. The strategic acquirers are circling.

This is exactly what the room at Wellist was telling founders to become. Chris is already there

Catching up with Chris Mirabile from Novos, where he shared with me details behind the exciting double-placebo study. More on this to come!

NAD, and changing my mind in public

Now the part where I had my mind changed in real time, which is supposed to be the whole point of going to a conference and almost never is.

I did a hot-takes session with my friend Dr Halland - longevity doctor who recently launched Cell Theory Labs (@celltheorylabs) and has been heads-down on NAD biology for years - and I went in with my standard skepticism. NAD is a category I have largely written off as overpromised, expensive, and oral-bioavailability-questionable.

Halland did not argue with my priors. He went under them.

The conversation moved through:

• Precursor distinctions (NR vs. NMN vs. NAD+ direct)

• The actual mechanistic case for cellular energy in aging tissues

• What the human data does and does not say

• Where the marketing has run ahead of the science (which is most places)

I left the stage rethinking whether I should have NAD support back in my stack. That is not a sentence I expected to type. Halland’s point that stuck: the molecule is not the problem; the delivery, dosing, and category discipline are.

This is the exact pattern that defines this entire moment. The substrate is real. The story around it is mostly noise.

A different kind of hot seat: Elaine Glass

Hot seat with Elaine Glass

The counterweight came in a hot seat with Elaine Glass, whose book Get Quiet: 7 Simple Paths to the Truth of Who You Are lays out seven paths inward, starting with awareness - the willingness to actually look at your own life instead of around it - and ending at a still point where the question is not what to add but what to listen to. After two days of talking about what to put in the body, sitting with Elaine was a hard reset. Her premise is simple and inconvenient: most of the answers we reach for in compounds and protocols are already in us, if we get quiet enough to hear them. I needed the reminder. Probably you do too.

So back to where I started

Three thousand years ago, my ancestors figured out that going from very hot to very cold made you feel better. Three years ago, my Oura ring told me the same thing.

The sauna hasn’t changed. What’s changed is that I now have:

• A personalized, AI-mediated, longitudinal read on my own physiology

• A research literature on contrast therapy that can be scanned in seconds

• A peer group of operators and scientists I can text mid-thought

• A market that has finally decided wellness is infrastructure rather than indulgence

That is not a small upgrade. But it does not replace the original technology, which was: do something hard, then rest, then do it with people you love.

The Blue Zones research has been telling us this for two decades. Harvard study confirms it. We are still acting surprised every time we rediscover it.

Nothing has changed. Everything is changing. The sauna is still a sauna. The needles are still needles.

Select event partners I got to sample!

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Appendix - Sources & Studies

• McKinsey & Company. (2025). The Future of Wellness 2025: Trends and Strategic Imperatives.

• The Future Laboratory × Together Group. (2026). Wellness: Trends, Opportunities and Strategies for Scale.

• Boston Consulting Group. (2024). Why Wellness Has Become A Massive Global Market.

• Euromonitor International. (2025). Beauty & Personal Care: Health-Positioned Supplements.

• Laukkanen, T. et al. (2018). Sauna bathing and risk of cardiovascular and all-cause mortality. Mayo Clinic Proceedings.

• Patrick, R.P. & Johnson, T.L. (2021). Sauna use as a lifestyle practice to extend healthspan. Experimental Gerontology.

• Yoshino, M. et al. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science.

• Martens, C.R. et al. (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications.

• Aliper, A. et al. (2022). Novos Core formulation effects on human dermal fibroblast aging biomarkers. (Novos Labs published research — please verify exact citation against most recent version before publishing.)

• Buettner, D. & Skemp, S. (2016). Blue Zones: Lessons from the world’s longest lived. American Journal of Lifestyle Medicine.

• Holt-Lunstad, J. et al. (2010). Social relationships and mortality risk: a meta-analytic review. PLoS Medicine.

I have since joined as an advisor. This is our first public conversation.

Petal is your tracker in the form of bra insert, as pictured above. link here.

Julia: Start with your background, because Petal is not your first company and the path here matters.

Anand: I fell in love with wireless communications very young, back when it was still car phones. By the time I graduated it was cell phones, and I ended up doing research on 3G and 4G protocols sponsored by Nokia Research Center. Then seven years at Motorola Mobility, where I worked on the 3G Razr, the platform that became Android, the first Android tablet, and something we called a smart watch before anyone used the word wearable. That was the Moto Active.

I moved to San Francisco because I was entrepreneurial and the VC infrastructure in Chicago wasn’t there yet. Worked at a few companies, including on the Jambox and at Lab 126, then started my first company in 2015. UJet. The thesis was that people communicate visually and contextually through smartphones, except when they’re talking to a business. I built that for almost ten years. The name is dedicated to someone I lost to breast cancer. Everyone around me, including my investors, knew I was going to come back to that.

Julia: So Petal was always the plan.

Anand: Always. I started looking more closely at women’s health and saw two major crises running in parallel. The first is cardiovascular disease. One in three women ultimately dies from it. Women live longer but sicker. They are dismissed at emergency rooms without proper cardiac testing at seven times the rate of men, and their symptoms present differently, what medicine calls atypical, which I find a frustrating term. Jaw pain, back pain, nausea instead of the textbook chest and arm. The second crisis is breast cancer, and the trend lines are going in the wrong direction. The largest relative increase in incidence is now in women in their 20s and 30s.

Julia: Tell everyone what Petal actually is, because even I had to see it to believe it.

Anand: Petal is a bra insert. It sits at a woman’s anatomical core, right over the heart and the fibro-glandular tissue. It uses bioimpedance analysis sensors, not the optical PPG sensors or temperature sensors you find in wrist and finger wearables. We are not shining a light and extrapolating from the blood flow response. We are listening directly to what the heart is telling the ventricles to do. The signal is the same as an ECG. That matters because it is more accurate, and because it does not require the hand to be still.

Every other wearable is designed around the assumption that you filter out movement. We don’t need to. Women move their torsos significantly less than their arms. So our signal quality during a workout, a commute, a stressful presentation, a walk pushing a stroller, is high when others are filtering noise.

Julia: Which is the part that got me. Most wearables are still essentially optimized for sleep recovery. You are going the other direction.

Anand: Exactly. Cardiovascular and cardiometabolic events happen during the day, under stress, during activity. Women wear bras for an average of twelve hours a day in our research. So the adherence is built in. It fits into the lifestyle women already have rather than asking them to build a new one.

The other thing that is distinct is style. A lot of women stop wearing wrist wearables because they are bulky, or they interfere with strength training, or the battery life drops off. This is invisible. You associate it with your sports bra, you use it for a workout two or three times a week, forty-five minutes to an hour, and you are getting real data measured at the source.

Julia: Walk me through what I am actually tracking.

Anand: Right now, heart rate, HRV, breathing, and adipose tissue composition through the bioimpedance sensors. That last one is significant. The breast is majority adipose fat tissue. Characterizing that gives you a proxy for midsection fat composition, which is more predictive of longevity risk and disease than BMI. It is also invisible. No scale. No number that follows you around.

The app shows you what zone you are in, accurate HRV, and real breathing data, not a timer but an actual visualization of your heart rate declining and your breathing pattern shifting when you do breathwork. The app was designed starting from women, not adapted from a male athlete use case after the fact.

Julia: And where is this going. Because the cardiovascular piece is the first chapter.

Anand: The second chapter is early anomaly detection for breast cancer. We are building the foundational model right now. Women were excluded from early clinical trials until 1993. Mice do not have a menstrual cycle. The data we have is not built on women’s physiology, and that is the gap we are filling.

Mammograms are a 2D rendering of a 3D organ. Over 50% of women have dense tissue, which means they get a letter after their mammogram saying the results may be incomplete. Our approach starts from 3D, from the breast in its natural form, characterizing tissue types, looking for deviation longitudinally over time. The head of breast radiation oncology at UCSF is part of the team. We have FDA clarity on the classification of the bioimpedance sensors. We are moving.

The goal is ambient. Technology that disappears into your life and builds a baseline specific to you, over time, that is actually useful when something changes.

Julia: Last question. Who are you looking to connect with?

Anand: Anyone obsessed with women’s health. Get the device, petal.today. Try it. The more women using it, the stronger the model, the stronger the mission.

Petal is available at petal.today. $199. Bra insert with app, two colors currently shipping.

That’s the question I keep coming back to every time I read another profile of someone who lost forty pounds on a GLP-1 and then, almost as an aside, mentions they also stopped wanting wine. And shopping. And the 2am spiral of should-I-or-shouldn’t-I. The food noise went quiet, and then, a little more quietly, so did everything else.

The science on this is genuinely interesting and genuinely incomplete, which is how most useful science tends to be. GLP-1 receptor agonists, semaglutide and tirzepatide specifically, don’t just talk to your stomach. They communicate with the brain’s reward circuitry. Nora Volkow at the National Institute on Drug Abuse has spent decades mapping exactly these dopaminergic pathways, the ones that make you reach for another glass, refresh the feed, text back too fast. GLP-1s modulate wanting itself. And they do it, from what the early data suggests, quite well.

Which should probably give us a moment’s pause.

I’ll say where I sit in this, since it’s relevant to the argument. I’ve been trying to answer this question for myself. Not academically. Personally. Sitting with whether to try them. And there’s a view I’ve arrived at that I find mildly inconvenient: if you work in this space and you haven’t tried the thing you’re forming strong opinions about, that’s a gap worth being honest about. Especially if you’re a doctor (which i’m clearly not!). The n=1 data point you’re missing is your own, and that tends to show up in the quality of the thinking.

So I remain curious, genuinely. And equally unsettled. Not by the mechanism. By the category. The idea of getting hooked on a pharmaceutical solution to maintain something I’d always understood as being about will, desire, the kind of person you are. That framing runs deep. Replacing it with a weekly injection feels less like an answer and more like a sharper version of the original question.

The premium wellness market spent decades building a very expensive infrastructure around a single idea: that craving was the problem. Too much appetite, too much indulgence, too much noise. GLP-1s are the logical conclusion of that project, delivered once weekly, subcutaneously, elegantly.

But here’s the thing. Desire is also, inconveniently, what gets things made. The longing that drives creative work. The hunger that makes someone call the person, stay in the argument, order the dessert and mean it. I’m not making a case against the drugs. That would be facile and also not my lane. I’m making a case for noticing what we’re framing as the problem.

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Because when “decreased interest in reward-seeking behavior” is listed as a side effect with quiet neutrality, we’re describing something more than a reduced appetite at dinner. We’re describing a modulation of how a person moves through the world. Research from Olivia M. Farr and colleagues in Diabetologia established that GLP-1 receptors exist in the parietal cortex and hypothalamus — brain regions with nothing to do with digestion and everything to do with how we process experience. A 2025 clinical review by Tveit and colleagues went further: GLP-1s increase serotonergic activity at the 5-HT2C receptor, the same pathway behind SSRI-induced motivational blunting and reduced sexual desire. The mechanism for quieting desire isn’t just theoretical.

The broader psychiatric picture is net positive and I want to be clear about that. Large population studies find GLP-1s associated with meaningful reductions in psychiatric hospitalization, not increases. This is not a story about a drug making people worse in the ways medicine knows how to measure.

What medicine isn’t measuring yet is this: those trials track hospitalization, adverse events, depression scales. They are not tracking whether someone stopped wanting to call the person, lost the pull toward the project that used to wake them up at 6am, or found the things they used to hunger for simply quieter than before. Those don’t register in any database. They’re the texture of a life. And they may be exactly what the 5-HT2C pathway is modulating.

The question isn’t whether these drugs work. They do. The question, and I think it’s the more interesting one, is what we believed was broken that made us reach for them in the first place.

We are all in search of something. That’s the whole premise. But it’s worth asking, occasionally, whether we’re searching for less wanting, or for wanting the right things.

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In Search Of covers the intersection of longevity science, culture, and the questions the industry isn’t asking loudly enough. No hype. No supplement stacks. Just rigorous thinking on what it actually means to build a longer, better life.

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References

• Farr, O.M. et al. (2016). GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia, 59(5), 954–965. PMID 26831302

• Volkow, N.D. & Koob, G.F. (2015). Brain disease model of addiction: why is it so controversial? Lancet Psychiatry, 2(8), 677–679. PMID 26249284

• Volkow, N.D. et al. (2025). GLP-1R agonist medications for addiction treatment. Addiction. doi:10.1111/add.16626

• Tveit, M. et al. (2025). Clinical review of how glucagon-like peptide-1 agonist obesity medications decrease sexual desire, and a biopsychosocial model for why we don’t ‘see’ it. The Journal of Sexual Medicine, 22(Suppl 1). PMC12704374

• Sa, B. et al. (2026). Psychiatric effects of GLP-1 receptor agonists: a systematic review of emerging evidence. Diabetes, Obesity and Metabolism, 28(1), 50–59. PMID 41126551

• Taipale, H. et al. (2026). Association between GLP-1 receptor agonist use and worsening mental illness in people with depression and anxiety in Sweden: a national cohort study. The Lancet Psychiatry. PMID 41862258

• Watabe-Uchida, M., Eshel, N. & Uchida, N. (2017). Neural circuitry of reward prediction error. Annual Review of Neuroscience, 40, 373–394. PMID 28441114

Spa at Verdura Rocco Forte Resort, Sicily, where I spoke at the Leadership in Retal Conference

Will we still be talking about longevity in 5 years?

I’ve been saying this for years. Longevity was always going to become luxury. Not in a weekend-retreat way. In a serious, where-is-the-smart-money-going, who-owns-the-next-decade way.

And now it’s arrived.

A few months ago I genuinely thought the word “longevity” had gone stale (and wrote about it here) - overused, stripped of meaning by brands slapping it on collagen powder and infrared saunas. But it’s back. And this time it means something different. The era of the solo biohacker optimizing HRV at 2am is winding down. What’s replacing it is harder to articulate but unmistakable if you’re paying attention - a move away from data fatigue, away from the quantified-self as personality, and toward something more integrated. More cultural. More, frankly, sellable.

The major luxury houses (think Loreal x Kering deal as example) don't make bets on trends. They make bets on the next century. When groups that built some of the world's most enduring heritage brands start allocating seriously into longevity - through partnerships, acquisitions, and internal investment - they're telling you exactly what they think the next heritage category is. These are not curious observers. They're acquirers.

Think about millennial pink. That wasn’t an arbitrary color trend. It was a precise cultural expression of where wellness was emotionally at that moment — soft, aspirational, faintly anxious. Wellness has always worked this way. It doesn’t lead culture. It mirrors it. And right now, culture is exhausted, overstimulated, and quietly desperate for connection. So longevity is following. The nervous system. Community. Saunas you go to with other people. Cold plunges that became social rituals. The shift isn’t random - it’s a direct reflection of what people actually need right now, dressed up in the language of health optimization.

Image from https://www.byrdie.com/millennial-pink-trend-revival-11679781

This is what the luxury brands are reading. Not the biohacking data. The cultural mood.

The industry spent years treating chronic stress as a productivity problem. Optimize around it. Push through it. The research is now catching up to what good practitioners already knew: dysregulation isn’t a mindset issue, it’s a physiological one. Somatic stress storage - how the body holds unresolved stress at a cellular level - is entering the longevity conversation whether the mainstream is ready or not. The science isn’t fully there yet, but the signal is impossible to ignore. The sheer volume of people reporting somatic releases, breakthroughs in bodywork, nervous system resets - that’s not anecdote anymore. That’s a pattern.

So. Will we still be talking about longevity in five years?

Yes. Just not the version we started with.

The word is being redefined in real time - away from the solo optimizer with a CGM and a supplement stack, toward something that looks a lot more like a cultural movement. That shift is already happening. The capital is already moving. Watch it enter the consumer and political mainstream the same way nutrition did. Slowly, then all at once.

Retail Hub Annual Conference - Leadership in Retail - at Verdura Resort, Sicily, with founder of the conference, Massimo Volpe.

Is Longevity The New Retail Category?

Short answer - yes.

I was recently in Sicily, speaking at a summit organized by the Retail Hub of Massimo Volpe - a room full of serious retail founders, department store operators, people who think about physical space professionally. Longevity didn’t squarely fit their world. And then after I spoke, the hallway conversations started. People running major flagship stores quietly asking: is this a retail category now?

Galeries Lafayette in Paris was earliest with their Wellness Gallery bringing french pharmacy beauty, wellness services and longevity curved into the department store. Ahead of the curve, by most accounts. (Sometimes being first and being right aren’t the same thing.) But the direction is clear. Physical retail is shifting from products to services as its primary value proposition, and longevity sits right at that intersection. The problem is that monetization hasn’t been solved. Services are entirely staff-dependent. And we have not yet produced a generation of floor staff who actually know how to sell wellness — to explain it, contextualize it, make it feel necessary rather than optional.

Nico Mermoud - HOKA founder - shared the origin story behind the brand! More to come on him in a follow up post! Send me any questions you want to ask him :)

Equinox had to build that capability from scratch. It took years and it was hard. Now we have more physical retail spaces selling wellness in the US than almost any other category, and the knowledge gap on the ground remains enormous.

That gap is exactly where the opportunity lives. It’s something I’m actively building toward. More on that soon.

If this landed for you, share it with someone who’s paying attention to where health is actually going. And if you’re building in this space — or just have a strong opinion about where it’s headed — I want to hear from you. Reply or find me. And if you’re not subscribed yet, now’s a good time!

My speaking entourage in Italy, aka my mom :)

Appendix: References

• Porges, S.W. (2011). The Polyvagal Theory: Neurophysiological Foundations of Emotions, Attachment, Communication, and Self-Regulation. Norton.

• van der Kolk, B. (2014). The Body Keeps the Score. Viking.

• Levine, P.A. (2010). In an Unspoken Voice: How the Body Releases Trauma and Restores Goodness. North Atlantic Books.

• Bower, J.E. & Irwin, M.R. (2016). Mind-body therapies and control of inflammatory biology. Brain, Behavior, and Immunity, 51, 1–11.

• Epel, E.S. et al. (2004). Accelerated telomere shortening in response to life stress. PNAS, 101(49), 17312–17315.

• Slavich, G.M. & Irwin, M.R. (2014). From stress to inflammation and major depressive disorder. Psychological Bulletin, 140(3), 774–815.

Hoan - high end dermatologists offering anything from stem cells injections and plastic surgeries to non invasive treatments. This is a picture from one of their rooms, right before I did SOFWAVE (more on it below).

Early this year I took an impromptu trip to Seoul. Partially because I was in the region, but mostly because it’s impossible these days not to see K-beauty (or Seoul procedures) overtaking my feed (if you don’t care about beauty recs - scroll all the way to the bottom)

I planned the entire trip in 48 hours.

Between a few (lucky) phone calls, local recommendations, amazing hotel concierge (Josun Palace) and running into equally unprepared friends from Miami (hi Chad & Steph) with equal determination to figure out the place (what to do and what’s fair to pay) - we figured out the system… quickly.

But here’s the thing: you need real self-esteem going in. This is not a sport for everyone. Before you even book a consultation, be prepared to hear - consistently and repeatedly - everything that’s wrong with you (especially given the Korean aesthetic of of perfection and glassy and “plumpy” skin).

Chad called it “radical transparency for your face” (borrowing from his former boss management style) and I honestly couldn’t come up with better description of how the trip felt.

The former I don’t need to explain, but the latter… skin is your largest organ, and it shows (many) internal imbalances of aging. Aiming to look good isn’t just vanity - it’s preservation in the darwinian sense.

Seoul is a city where grandmothers still practice 400-year-old herbal medicine next to spotless clinics and dermatology offices that look like Apple Stores. Hotel lobbies full of tourists with bruised faces from plastic surgeries (you get used to it) and fashion that doesn’t take itself too seriously - I AM SOLD.

I would divide Seoul into 3 (wellness) categories:

1. Can do in the US, but here it’s cheaper (quality on par with top US clinics)

2. Can’t do in the US due to legality

3. Wellness culture just done better and more affordable

Below is my full itinerary:

Tamburins store - Gentle Monster’s 1/4 brands - this one is all about perfumes. Perfumes a side, the design is absolutely worth going for)

The Beauty Concierge Question

I wasn’t in the market for anything big - spending $1K+ for help, on top of treatments didn’t make sense for this trip. That said, there are beauty concierge services in US you can hire if procedures are your main goal, and in many case very much worth the price (here is someone that was recommended to me). They know who’s best for what, especially if you’re moving toward invasive work or plastic surgery. Most places don’t speak English, so concierges handle scheduling, translation, and matching you to the right practitioner.

I personally built my schedule from recommendations and had hotel concierge schedule it all.

One thing I learned fast: places I found on Instagram advertised by US influencers were not good. Overpriced, underwhelming. This is based on two visits, but still - trust the local lists and people, not the algorithm.

Day One: Aquafield

I landed on a red-eye and went straight to Aquafield in Goyang before hotel check-in. $18 for 6 hours lying in semi-warm spaces watching nature projections. It’s where locals go to destress from the city. I left after two hours because I got bored, but it did the job of post-flight decompression. I do wish some of the sauna’s were hotter but alas!

There are many brunches of Aqufield, but this one apparently is the nicest! If you do go there I highly recommend the food hall in that mall.

Day Two: CESTIQ Face Contour

CESTIQ SPA is famous for their painful hand-slimming facial. Using just their hands, my face got slimmer - and bruised. They told me not to eat for two hours. It hurt. It worked. But like any non tech treatments - results come from regular use.

Pre and post the massage - other than big invisible bruises, less than hour later I noticed much more defined cheek bones!

This is the menu option I chose (which apparently is the most painful - it was - but I felt like practionair went easy on me clearly seeing i’m a tourist. You also are asked to change in this outfit which is a style I have seen in 5 different contexts in Korea.

Day Three: Facial Acupuncture at Kyunghee Hyojeon Clinic

Friday morning was Song at Kyunghee Hyojeon Clinic for facial acupuncture. Song developed her own technique. She treated one side of my face first so I could compare in real time.

This wasn’t spa relaxation. It felt like neuromuscular training. My face didn’t just look different - it felt plumpy!

The protocol: seven weekly sessions to train facial muscles, then maintenance monthly. Cost in Korea: $68 per session. Same treatment in New York: $500+. That pricing gap makes a different for sustainable wellness. That said, if you compare this to price of lifelong botox and fillers - might be in fact worth it.

The abdominal acupuncture that followed was intense - or to say it differently, had I known what is about to happen, I would 100% said no (below is an image of a needle that went into my stomach so you can understand). Dr Song - with whom I now text in case anyone needs a referral - also created a custom herbal mix for me and sent it to hotel - and I have to say - it helped me a lot!

Facial acupuncture - I did 20 min first on one side only to see if I can actually see and feel the results. I DID - the skin felt very toned and different - sadly, not something you can see on a picture.

This is 뜸 (tteum) - called moxibustion on my stomach that helps with all stomach issues and digestions.

Later: Glossy Skin Consultation + Treatment

Glassy Skin is the place you’ve seen on Instagram and TikTok. They do a full facial scan - detailed imaging that makes it feel clinical and measurable. If you’ve seen a Korean derm clinic on social, it’s probably this one.

I went in planning to do treatments after the scan. But the consultation quickly moved toward $3,000+ in recommended procedures - pricing closer to US rates than what I’d been seeing elsewhere. When I decided to leave, the pricing suddenly became negotiable, which told me everything I needed to know.

Sometimes the best treatment is walking out.

The face scan shows you your skin problems not visible easily - from deep sun marks to under eyes due to “too much screen”, you see it all. Worth nothing, this type of scan is not unique to Korea and you can find it in US or Europe.

Day Four: Numero 1 Scalp Treatment

Saturday afternoon was Numero 1, a 90 minutes of scalp treatment combining head massage and hand massage. The scalp work felt methodical, targeted, different from typical spa treatments. I loved it! Wish I could do it on a regular in US!

Later: HOAN: The Premium Derm Experience

HOAN was my favorite - and the most expensive. Stunning two-floor design, beautiful area. Everything is still at least 50% cheaper than the US, but this is where treatments felt truly premium. One doctor, one translator and what looked like 20 treatments rooms and many “nurses” - this was a well run operation’s place!

This is where I would have gotten Rejuran (salmon sperm injections), but I was too afraid of the pain and they didn’t sell it well enough for me to commit.

They sent full pricing upfront (via whatsapp). I met with the doctor, discussed goals. What surprised me: they didn’t push what I initially planned. No upselling. They suggested different treatments. It felt consultative.

But the overall price level was higher than I was emotionally ready to commit to in that moment. Even without pressure, the options created overwhelm.

I ultimately did Sofwave. Partly because it’s cheaper than the US. Partially because it’s what a friend I trust recommended (Hi Tara) and partially because I was flying that night and panicked about downtime from more aggressive treatments. I wasn’t sure about swelling before getting on a plane.

Sofwave felt like the safest, lowest-regret decision under time pressure.

Results: Absolutely LOVE IT!

** From google: Sofwave is an FDA-cleared, non-invasive cosmetic procedure using proprietary SUPERB™ synchronous ultrasound parallel beam technology to lift and tighten skin. By generating heat in the mid-dermis (1.5mm) to stimulate collagen and elastin, it reduces fine lines and wrinkles on the face, neck, and chest with minimal to no downtime.

Day Five: Spa Gogyeol

Thursday evening was Spa Gogyeol: body scrub plus massage. It was fine. Good, even - ended up serving the “post flight debloat / lymphatic” purpose without being that. But $300 for 90 minutes isn’t a steal, even in Seoul. Not worth it. I also, personally, get extremely board with anything over 60 min (and there wasn’t a single treatment with this length!)

Later: Christian UNV Head Spa

Sunday morning I did Christian UNV Head Spa - 75 minutes of what they call “head thinning treatment.” This was my favorite experience of the trip.

They photographed my scalp before starting, had me change into (very cute) treatment clothes, then did the full treatment followed by another scan to show what changed.

I lay in a reclining chair with warm water streaming over my scalp (see below), eye mask blocking all light, red-light heat on my belly, simultaneous foot and arm massage. The scalp scan showed I have three hairs growing from single follicles - apparently excellent for density.

The treatment + the outfit you get changed into (very Hill house vibes if you ask me)

Not sure that the actual scan did much - cool to do once and never again - but the experience itself was top notch - it felt luxurious and cosy at the same time. The most shocking part for me was that, despite whole shelf of sculp cosmetics, I wasn’t offered to buy any of them (a little sad in retrospect as I would have gotten a few things!)

Even the animals are getting skin care love in Seoul!

What I Actually Brought Home

All the products I bought at Olive & Young

(Non Beauty) Products:

• Japanese raisin (aids alcohol metabolism, tastes incredible)

• Black bean tea (daily routine now)

Beauty Products

• Korean face creams—very clean formulations

Fashion:

• J.Rium: Cashmere-blend basics, clean design

• Leha: Looks high-end, priced like COS. Current favorites.

• Coor: Korean Acne vibes minus the jeans

• Fox Vintage (Gangnam location): Koreans don’t value vintage. You will. Shockingly cheap.

• Gentle Monster Haus Nowhere in Seongdong

• Point of View: the cutest stationary store

• LOEWE Cafe: somewhat new but worh visiting for the experience and decor

Coor store (local brand)

Unlike what it looks like, everything on this picture is edible and it’s a dessert. The Cafe at Gentle Monster store in Seongdong

Didn’t Do But Wish I Did:

• Realign Official

• The (painful) ear pilates

• Riverhillspa

• KUDO Derm (Kim K’s Clinic)

Food & Non-Wellness:

• Josun Palace brunch: Legendary even if you don’t stay there

• Mr Ahn: Creative Korean tasting menu (thanks to Eric Ripert from Le Bernardin for an awesome list)

• Gebangsikdang: Amazing crab - prepare to get messy!

• 압구정진주 한남직영점: locals only korean bbq (need to put like this in google maps)

• Yeongdong Jang-eo & Mirak: Freshwater eel restaurant, was truly the most memorable meal (outside of Mr Ahn); very fancy

• The Cafe at Gentle Monster store in Seongdong

• Byeokje Galbi the Cheongdam - fancy (and excellent) Korean bbq

• Zest Soul: Amazing cocktails. On the World’s Top 50 list, which is often risky, but this one delivered.

Museums / Art:

• National Museum of Modern & Contemporary Art

• Leeum Museum of Art

• Amorepacific Museum of Art

The Josun Palace fitness & wellness was absolutely amazing. Reformer studio overlooking the city, gender sauna, pools and steam rooms, as well as beauty counters with latest products to try. It was also very clear this was hotel for the locals as the place has a membership

If you need recommendations (outside of what above) please reach out!

If you liked this newsletter or if someone you know does, please share, comment, subscribe!

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And as someone who witnessed Noma’s fermentation revolution firsthand, Ben understands how a restaurant’s internal experiments can grow - often in strange and unexpected ways.

Here’s what struck me about Ben’s story: he’s been observing a form of health innovation for decades without calling it that. While longevity science was catching up to the benefits of fermented foods, seasonal eating, and dietary diversity, chefs like René Redzepi were already solving for it - not because they read the research (though they were often the ones writing the research papers), but because constraints forced creativity.

The question I kept circling back to: what does someone who watched Noma’s food revolution from the inside see that the wellness industry is missing?

Ben Liebmann

Julia: You’ve had this fascinating career arc - music, television, hospitality. What’s the through line?

Ben: Creative people. Creative industries. I’ve spent 25 years working with extraordinary creative people. There was no business case behind what drove me to these industries—it was purely driven by gut and heart.

I left college and went to Warner Music at what I describe as “the end of the heyday and the beginning of the disruption”. I was there when Napster arrived and saw what real disruption looked like from the inside. I left the music industry when I wasn’t loving it anymore, when it felt like it was becoming more of a job. The moment I left, my love of it came back.

Then I went to Fremantle and was working for them when MasterChef launched in Australia. The media was up in arms: “Nobody cares about watching cooking in prime time”. Some pundits suggested this would become the biggest failure in Australian television history. It became the highest-rating show in Australian television history. That was the first time I saw the power of food to entertain and inspire. Within five years, that show was being produced in over 50 countries and broadcast in over 100 around the world. That’s how I started connecting with chefs. Many of the world’s best had been part of that show - Ferran Adrià, Daniel Boulud, Thomas Keller, Gordon Ramsay, Anthony Bourdain, René Redzepi.

Noma | credit: Ditte Isager

J: How did you end up at Noma?

B: René and I met through this sliding door moment and got to know each other over two to three years. I was living in London, traveling to Copenhagen each year to attend the MAD Symposium - his gathering where the most important minds in food (chefs, farmers, academics, authors, etc) would discuss the future of the food system. Not just what we’re eating, but how we’re going to create a working system that supports the planet.

In 2015, René was doing the first Noma popup in Tokyo, and I stopped by on my way back to Sydney. We were sitting at the bar after service one night, and he talked about how well it had gone and wanting to do it again. What do you think about Australia?” I said, “Yeah, of course you should. It is a food and restaurant obsessed country” He said, “Then you help us. You do it.”

I thought I was doing it as a project and then I’d go back to television. Six months in, he said, “When this is done, I think you should move back to Denmark.” So my family packed up the shipping container we’d just unpacked from London. I was with René and the team as COO of Noma for seven years.

Noma | credit: Ditte Isager

J: Noma Australia - 5,500 tickets selling out in three minutes - what did that tell you about where food culture was heading?

There was research you mentioned to me showing Gen Z and beyond would look to what they ate, where they ate, and the people who were cooking it for them, to define and who they were to the world - the way previous generations had done through fashion, music, sporting teams. Food was becoming part of our identity.

And here’s where I want to dig in, because what Noma was doing - the fermentation, the foraging, the seasonal constraints - turns out to be exactly what longevity science now tells us we should be doing for our gut health (or metabolic flexibility). But you were watching it happen for completely different reasons. Walk me through what René was actually doing!

B: That’s a misconception people have. The pillars of Noma’s creativity was driven by constraint. Fermentation initially was about preservation. Noma opened in November 2003, followed by one of Denmark’s coldest winters. René would tell the story - the ground was so solid you couldn’t grow anything, not even root vegetables. They turned to fermentation to preserve ingredients for the following seasons.

What they found was that through preservation, they were unlocking new flavors. That curiosity - René will tell you curiosity is the most powerful tool of any chef—led them to keep exploring.

J: And the foraging?

B: Foraging was intertwined with the New Nordic manifesto: cooking only what grew native to where you were. Time and place. For a restaurant in Denmark, that meant no citrus, no olive oil, no spices. Things we take for granted were suddenly out of the restaurant’s pantry.

I believe René was given a Swedish survivalist’s book about how to survive on the land in a post-nuclear Europe. He started tasting and foraging his way across the wild landscape.

Through fermentation and foraging, a new pantry was created. A new language was created.

Salad with dried berries and herbs with warm chocolate sauce, summer 2025 menu | photo credit: nomacph

J: And the famous ants on a shrimp dish?

B: The ants weren’t done for art. Chef Alex Atala had taken René into the Amazon and taught him that first nation’s people would eat ants - the stomach enzymes replicated the flavor of citrus. Suddenly René had citrus in his pantry through Danish wood ants. It was problem-solving, not performance.

J: So René accidentally built what we now know is one of the most gut-healthy, nutrient-dense approaches to eating: fermented foods, wild foraged plants, extreme dietary diversity, seasonal rotation - all because he was solving for flavor under constraint. That’s fascinating to me because the wellness industry is trying to convince people to eat this way with data and studies, and he just made it delicious and desirable. You’ve said chefs should be change makers for some of our biggest challenges. This feels like proof.

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If you decide to stop reading this newsletter here - this is my conclusion on the topic:

If you want to take care of your health in 2026, nervous system regulation is (definitely) the place to focus.

But there is as much art as science as to the how - or to say it differently, you actually cannot (fully) biohack it.

Here’s why it matters: Nervous system is the communication network between your brain and body that controls everything from heart rate and digestion to immune function and stress response, constantly assessing whether you're safe or under threat

Blue Monk an image made for a custom tea blend from Gentle Monster’s cafe brand Nudake; next to it a dessert in vegetable form, which definitely messes with your senses! If you have SEOUL longevity recs, send my way!

When it’s dysregulated, everything else fails: your sleep, your immune system, your ability to recover from stress, even how well your body receives the supplements and protocols you’re investing in.

And for certain personality types (👋 Type As), it's often hard to spot when it's dysregulated until we hit a wall: burnout, unexplained fatigue, constant colds, weight gain, you name it.

But the answer isn’t: stress less…

…in fact, many of us (hi Type A again) learn to operate only in fight-or-flight mode, making it our default state where we don’t even register feeling stressed anymore.

It’s also not about eliminating stress but about building resilience so your body can actually bounce back from stress into true parasympathetic relaxation. Stress is good (evolutionary speaking)

Let’s dive in.

Read to learn why it’s misunderstood, what Covid and nervous system dysregulation have a lot in common and how to think about it, why supplements and protocols timing matter, our recent event on the topic in NYC and my personal (mostly Equinox) recs I go to in NYC to optimize my system.

Disclaimer: This post is inspired by early proponents in the longevity space of topic such as our Dr Tamsin Lewis (who even coined the term Wellgevity to account for exactly that), as well as learnings from of the recent events we did with Dr Sogol Ash and The Altar (sign up for waitlist here), and of course my own health!

The Problem: We’re All Running From Bears

I’ve been on my own longevity journey for years - not enough energy, gut issues, the works. I’ve had COVID five (?) times - hard not to pinpoint when my health issues really started.

Here’s the thing: I’m not alone. There’s probably a reason this video by went viral on Substack with half a million views: people are connecting dots between viral exposure and what feels like accelerated aging.

And here’s where it gets interesting: your mind, nervous system, and immunity are completely intertwined. Viruses like SARS-CoV-2 aren’t just temporary infections. The spike protein attacks ACE2-rich tissues-lungs, heart, blood vessels-causing long-term vascular damage and cognitive decline. ORF8 disables your interferon signaling, allowing the virus to evade detection while triggering massive inflammation.

This leaves your immune system in chronic activation - exhausted, dysregulated, prone to autoimmunity. The result? Immune burnout. Chronic inflammation. Mitochondrial dysfunction. The exact cascade that tanks your nervous system and keeps it stuck in threat mode.

As part of our ongoing programming residency at 113 Spring in NYC (go check it out), last week we hosted an event on exactly that topic with Dr. Sogol Ash and The Altars’ founders Sheba Jafari and Henrique De Castro. The biggest pattern Dr. Ash sees in founders and high performers confirms it - its not lack of discipline or taking care of themselves. It’s a dysregulated nervous system despite all that.

And here’s the catch: if your nervous system is stuck in threat mode, your body won’t receive the supplements, peptides, or protocols you’re throwing at it. The system needs to feel safe enough to heal first.

What to Actually Do: You Can’t Biohack Your Way to Safety

Here’s what I’m learning from Dr. Tamsin Lewis, our head of expert community - most of us are approaching this backwards. We think nervous system regulation is another thing to optimize - breathwork sessions, therapy appointments, yoga classes, wearables, protocols. These tools help. But they’re not the foundation.

This is why so many high-functioning people keep adding more tools and feel increasingly dysregulated.

Your nervous system doesn’t respond to optimization. It responds to conditions. When your body consistently receives signals that its environment is predictable, relationally safe, and metabolically supported, regulation emerges naturally.

What this actually looks like? Movement that feels supportive rather than punishing, self-compassion that reduces internal threat, nourishing connections, play and laughter, shared meals. Your heart rate variability (HRC), vagal tone, and immune signaling respond to these conditions just as powerfully as they respond to advanced techniques.

Here is a list I pulled from Dr Tam and others in this space:

Start with the foundations:

• Sleep: Aim for 90+ minutes of deep sleep - that’s when repair and immune function rebuild

• Protein in the morning: Signals safety, stabilizes blood sugar and cortisol

• Daily downshifts: 20 minutes before bed doing anything that doesn’t require you to be “on” (that means, don’t wake up and scroll your thing first thing)

• Movement that feels supportive: Strength training that signals vitality with focus on breathing, not workouts that feel like punishment

• Nourishing connections: Shared meals, play, laughter - oxytocin matters for REM sleep and bonding

• Self-compassion: How you talk to yourself creates or reduces internal threat

Then add targeted support:

• Vagus nerve work: Breathwork, humming, or tech like Pulsetto

• Sauna 3x/week: 20 minutes of actual sweating for parasympathetic activation and immune support

• Reduce cognitive overload: Less doomscrolling is a good start

Support immune and mitochondrial function (especially post-viral):

• NAD+ precursors (1MNA, NMN, NR): Mitochondrial repair and cellular energy

• Polyphenols (Resveratrol, Fisetin, Quercetin): Natural senolytics that clear damaged cells

• DHA (Omega-3s): Repairs vascular damage and reduces neuroinflammation

• HBOT: Restores immune function and repairs viral-induced inflammation

• Thymosin Alpha-1: Boosts T-cell function and reduces chronic inflammation

And then there are peptides (which I’m pro, as long as you can verify your source and your vial, an impossible task when all of this is coming from China. Here’s an article from NYT on just that).

Get the data:

• HRV (Heart Rate Variability): tracks your nervous system’s ability to shift between sympathetic and parasympathetic states. Mine sits below 30 when it should be around 100. Oura, Whoop, Apple Watch etc. measure it

• Cortisol patterns: DUTCH test, or at-home devices like ElI Health or Lumen

• Blood work: cortisol, or inflammatory markers through Function Health

  • Tip: look at your DHEA levels on next blood test. DHEA is the precursor to all your hormones and when it tanks, your body is telling you it is interpreting everyday life as danger.

• Feelings: “Not feeling like yourself” or “not 100%” is equally as valid data point

My NYC Spots

HBOT (hyperbaric):

• Equinox Domino

• Extension Health

• NextHealth

Sauna:

• Equinox Hotel Spa

• Equinox Hudson Yards (female locker only)

• Equinox Domino

• Equinox Park Ave (infrared; side note compression boots and red light therapy is part of the membership in this location - a hidden secret; yw)

• Clean Market Battery Park or 54th (infrared)

• The Altar (opening soon) - I am biased as founding member but go sign up!

  Dr Sogol Ash & Sheba talking about nervous system regulation at 113 Spring

Bottom line: Many complaints - anxiety, exhaustion, brain fog, gut issues - are less about mindset and more about autonomic load. The system isn’t broken. It’s asking for support.

Repair begins when your body can downshift without bracing, and when everyday demands stop being interpreted as danger. That’s what 2026 should be about.

• The new food pyramid flipped upside down in US (South Park predicted this chaos 11 years ago - seriously worth watching)

• ChatGPT went into healthcare (for consumers); Anthropic followed with AI for Healthcare day after

• The FDA softened wearables regulations (peculiar timing!)

• Torch - a four-person team - got acquired for $100M (and why I might have to eat my words when I said that data aggregation is not a business model ;))

These aren’t isolated incidents. They’re signals that health consumerization is moving faster than regulatory bodies and doctors want it to.

And that’s the point. So let’s dive in

The Food Pyramid Gets a Rebrand (Finally)

Let’s start with the inverted pyramid. After 82 years of grain-lobbying disguised as nutrition science, the US government finally acknowledged that maybe, just maybe, prioritizing 6-11 servings of bread daily wasn’t optimal metabolic advice.

The 2025-2030 Dietary Guidelines flipped it: protein, dairy, and healthy fats at the top. Whole grains relegated to the narrow base. Added sugars explicitly called out as something to avoid, not “limit.” This is progress.

It’s been interesting watching the divide online - some people are ecstatic, other calling it equal hypocrisy (here is a good watch).

My opinion? We are arguing over the wrong thing - the universal guidance on nutrition makes no sense anyways.

Do I love that giant block of cheese sitting next to red meat and vegetables at the top? 🧀 🧀🧀 Not particularly. But I can find a study to support it. In fact I can find study to support any and all diet approaches from ketogenic to high carb and everything in between - and that’s why half of the arguments are not relevant.

Nutrition and its impact on each individual is highly complex - we are all individual beings with wildly different and changing factors that affect our metabolism. So the argument over whether meat and cheese should be on the top, is a true waste of energy IMO.

However the move towards minimally processed foods is a huge and necessary upgrade. Real nutrients, prioritizing protein, minimizing added sugars - all a directional win for the guidelines!

Big congrats to companies like EatReal.org and advocates like Dr Mark Hyman who’ve been lobbying for real food for years. This shift didn’t happen in a vacuum - it took sustained pressure from people who understood that the old pyramid was making us sick and that is a reason to celebrate. 🥳🥳🥳

Here’s the real part: the new design of the pyramid might matter more than the content shift!

Debbie Millman, chair of SVA’s branding program, eviscerated the visual execution in STAT, calling it “emoji-inspired clip art from a 1950s health pamphlet.”

She’s not wrong. But…

The fact that the government is even thinking about branding and visual communication for health guidance is proof that health has truly entered the consumer arena (here is Calley Means talking about it)

People are visual. If you want them to do something, make it look good. Make it feel modern. Make it shareable.

And case in point, this inverted pyramid? It’s generating discourse, criticism, memes, and most importantly, awareness. That’s consumerization at work!

In general, Health as a Political Topic Means More Confused Consumers

When RFK Jr. is unveiling dietary guidelines and the MAHA movement is influencing federal nutrition policy, health has officially become a political football.

That should worry us, right? Not necessarily.

Political attention (even messy, controversial political attention), accelerates consumer demand for clarity and solutions.

When the government says “eat protein,” people start asking: How much? What kind? Does this apply to me?

Confused consumers create demand. Demand drives innovation. Innovation attracts capital. The private sector delivers. This will probably be the most accelerated year in health tech innovation ever. That's exciting!

ChatGPT Health: The Reviews Are Mixed, But The Trend Is Clear

ChatGPT launched GPT Health and the internet lost its mind. The move makes sense: 230 million people weekly already ask ChatGPT about health and wellness. Being able to give personalized answers based on actual personal data? Obvious next step. Easy data integration across all your disconnected health outputs? Overdue.

Hard not to notice the new soft pastel tones. Are females the primary demographic asking those 230M weekly health questions? The design team's answer: obviously, so here's your millennial pink interface.

The skepticism is real. AI can give wrong or harmful guidance. Research shows AI learned to be persuasive - what a doctor sees might differ from what someone with zero medical knowledge gets, and there’s no way to control it. Data privacy concerns are valid, though maybe that’s the trade: privacy for personalization. We gave Google our location for better search results. This isn’t THAT different.

Good reminder however that right now ChatGPT Health isn’t replacing doctors. It’s an integration play. Better pipes, cleaner UX, faster answers. Diagnostic is not care. But diagnostics enable care.

Also to debunk other narrative going around - consumer health companies aren’t dead. The ones selling “data aggregation dressed up as care” are (though Torch just sold exactly that to OpenAI for $100M, so maybe I’m wrong). The companies that survive will treat ChatGPT as the front door, then win on longitudinal delivery, behavior change, and trust.

A great interview in the Information with and Dan Battelle on the topic of ChatGPT and broader implications. Listen here, start around minute 33.

Then This Happened: FDA Softens Wearables Regulation

Same week as the ChatGPT Health launch, the FDA announced it would limit regulation of health and fitness wearables.

The timing is fascinating. ChatGPT is entering the most valuable data collection play ever, your biometrics, while still defending itself from mental health support fiascos. Rules to use and sell this data? Not ready. Yet the FDA softened regulations anyway.

To me, this signals even regulators realize consumerization isn’t slowing down. Oura partnering to track migraines. Breath-based glucose monitoring (PreEvnt) entering trials. An explosion of devices measuring everything is coming.

The question isn’t whether technology advances. It will. The question is whether data governance keeps pace. It won’t. Problems we’re not ready for are coming.

The Real Story

All of these signal the same trend: health is moving out of the exclusive domain of doctors, regulators, and institutions.

Consumers want control. They want data. They want personalized solutions. And companies are racing to give it to them.

The regulatory bodies can’t keep pace. The medical establishment doesn’t want to. And that’s fine. The consumer will win anyway.