Restore Youthfulness & Vitality to the Aging Brain & Body | Dr. Tony Wyss-Coray

We exposed aged mouse brains to youthful circulation and watched dormant stem cells switch back on, inflammation ease, neural activity rise, and—most striking—memory come back online.

Welcome to the Uberman Lab Podcast, where we turn solid science into everyday tools. I’m Andrew Uberman from Stanford, and today I’m joined by Dr. Tony Weiss‑Korey, a leader in finding blood‑borne factors that can slow or even reverse organ decline. We cover youthful and exercise‑induced proteins, non‑linear aging and organ clocks, and practical levers like light, fasting, hormones, exercise, and social connection; this is the real biology of rejuvenation, not hype—so let’s get into it: what did the classic young‑to‑old blood experiment show, and what, if anything, maps to humans?

Using parabiosis—joining a young and an old mouse so their blood mixes—Tom Rando showed old muscle could behave young again, and we saw parallel gains in brain plasticity and memory. That pushed us to ask whether age‑shifted blood proteins drive aging or merely mirror it, and the data point to causation.

Most of us treat blood as a readout, but you’re saying the molecules in it can act like medicine.

Exactly—circulating proteins don’t just report status, they tune it, and their mix swings dramatically with age. You can even estimate someone’s age from their proteome, which is why the field is hunting the key drivers we could use to keep organs functional longer.

What’s the closest human analog to parabiosis so far?

We started Alkahest and, with Grifols, fractionated pooled human plasma, found brain‑active fractions in mice, then ran small trials in Alzheimer’s and Parkinson’s patients that looked encouraging. Grifols also showed therapeutic plasma exchange with albumin yielded cognitive benefits in a large, blinded Alzheimer’s study, and a separate small study in healthy older adults reported organs that tested biologically younger via epigenetic clocks; it’s early, but the signal merits larger trials.

Mechanistically, is young blood neutralizing accumulated damage or delivering pro‑youth signals?

Both—aging raises inflammatory proteins that impair cognition, and blocking some of them helps, while youthful pro‑growth cues reactivate repair programs. The hard part is the recipe: different cells respond to different factors, mitochondria are frequent targets, and single‑cell data show widespread but tissue‑specific resets; for what it’s worth, you don’t need to bank your own blood—pooled young plasma worked in our studies.

Does the Dracula folklore have any real scientific roots here?

Probably just the primal link between blood and vitality; nobody’s shown benefits from ingesting it, and we haven’t tested that, though history is full of crude blood‑related remedies.

Do organs age in sync, and how does that shape targeting?

They drift at different rates, and we can now build organ‑specific clocks from blood by tracking proteins that originate in each tissue. The gap between your calendar age and your organ’s biological age predicts future disease risk for that organ.

Can people get that kind of test today?

Through Vero Biosciences we built Vero Compass, which blends proteomic signatures with clinical and wearable data to flag your most vulnerable organ, guide personalized interventions, and retest to see if the organ’s age actually shifts.

So you could see how a new med—say for attention or lipids—changes organ age in real time.

Right, and in diseases like Alzheimer’s it could help stratify subtypes so we test the right drug earlier in the right group instead of failing broad late‑stage trials.

Quick reality check on NAD boosters: any proof that NMN, NR, or NAD infusions extend lifespan in humans or even deliver clear healthspan gains?

No human study has shown lifespan extension, though animal data suggest benefits and one trial confirmed these supplements raise blood levels. Quality control is spotty—NMN can be unstable—so if you try any supplement, insist on solid sourcing and third‑party testing.

People often mix up vitality and longevity—puberty accelerates change, and hormones like testosterone or growth hormone can boost energy but may shorten life; can we have both?

This is antagonistic pleiotropy in action: what’s great in youth can harm later, and evolution mostly selects for reproduction and child‑rearing, not long healthspans. We even see “waves” in the blood proteome—big shifts around the mid‑thirties—so the aim should be preserving function, not just adding years.

Name a few promising youthful factors and where they act—genome, epigenome, mitochondria?

Candidates include GDF11 and, in some contexts, IGF‑1; notably, plasma from exercised young mice outperforms sedentary young plasma. We and others traced some of those gains to liver‑derived signals like clusterin and GPLD1, showed recombinant clusterin can mimic parts of the exercise effect, and even found calorie‑restriction plasma transfers benefits—clear signs of organ‑to‑organ crosstalk that lands on energy systems like mitochondria.

Movement seems to feed the brain, not just through stress‑adaptation but by releasing helpful signals; on a personal note, what do you do for exercise?

I run outdoors two times a week for five to ten kilometers and do a bit of morning Pilates; the sun helps my mood too.

Why do kids heal so fast while older adults scar and stall?

With age, immunity tilts toward nonspecific, pro‑inflammatory responses, and the tissue matrix tends to overproduce components like collagen, so repair gets noisy and less coordinated.

How do we move from correlations to real pro‑health therapeutics, and what’s the timeline?

We need rigorous factor‑by‑factor testing in animals, then blinded, well‑powered human trials; proteins like klotho are advancing toward the clinic, but expect organ‑specific treatments rather than a single panacea, with first validated options plausibly within five to ten years.

Cautionary note: people self‑inject unproven factors or stem cells and get hurt; please do not do that.

Fully agree—mouse success does not equal human safety, and dosing, purity, and real outcomes must be established in controlled trials before clinical use.

What’s the real story on platelet‑rich plasma?

PRP concentrates your own platelets, which are packed with growth factors that can aid healing; it’s widely used in sports injuries and certain procedures, though benefits vary by condition.

And exosomes—what are they good for?

They’re tiny vesicles shed by cells that carry proteins, RNAs, and lipids; they circulate in blood, may serve as diagnostic messengers, and are being explored therapeutically, and our proteomic assays capture much of their cargo.

What about slow‑burn exposures—EMFs, plastics, low‑dose radiation—that might add up over time?

It’s tough science—many man‑made compounds appear safe acutely but could interact or accumulate; we lack clean long‑term answers, so prudence without paranoia is wise.

I try to limit plastics and eat mostly whole foods; organic versus conventional seems messy, and rural pesticide exposure worries me more than city air in some cases.

You can drive yourself crazy chasing purity, but cooking fresh and growing some of your own food, if you can, reduces unknowns—and agricultural exposures have been linked to disorders like Parkinson’s.

Let’s hit fasting: definitions are fuzzy, but does it help in humans, and how might it work?

Animal data show broad benefits—from lower inflammation to better proteostasis and oxidative stress—but monkey studies are mixed and we lack clear human clinical wins, so translation remains uncertain. Mechanistically, many cells reprogram energy use, and some effects likely ride through mitochondria and immune pathways.

Do you fast yourself?

I’ve tried a fasting‑mimicking diet for five days at roughly a thousand calories, felt sharper in ketosis, but I don’t know the long‑term payoff; day to day, an overnight pause from food is probably the most realistic lever.

I tend to have caffeine and water until late morning and eat dinner earlier; constant snacking seems worst for me. Before we close this section, sleep matters too—glymphatic clearance ramps at night—so are there known differences in that system between young and old brains?

Lymph looks like the body’s trash lane the blood misses, full of waste, so I’m curious what changes with age. If mice are tough, why not compare cerebrospinal fluid from younger and older people to see what tracks with cognition?

We infused young mouse CSF into old mice for a month and saw better memory, with oligodendrocytes emerging as key responders. In people, profiling thousands of CSF proteins in three thousand individuals revealed a synaptic‑protein ratio that powerfully predicts cognitive resilience or decline from early adulthood, independent of classic Alzheimer’s markers.

Causality is hard, but the longevity edge in fast‑twitch sports makes me wonder about sprinting versus endurance chemistry. Maybe explosive work sends signals that keep neurons and myelin support running strong.

There’s evidence for that: a lactate‑linked metabolite called Lac‑Phe spikes with all‑out efforts in animals and humans, has an identified receptor, and mediates benefits in models. Exercise trials are tricky since you cannot blind them, and whether you love or hate the effort likely changes brain signals.

Choice changes biology; forced running in tethered rats raises chronic stress and impairs memory, while voluntary effort helps. I do short, brutal intervals I dislike because they pay off, and I’d love to compare CSF and blood after high‑intensity versus long endurance work in humans.

Lifestyle has real leverage on dementia risk, but cognitive drills in already impaired patients mostly underperform, and individual appetite for novelty likely shapes benefit.

Pick challenging things you willingly do; use‑it‑or‑lose‑it applies to circuits as much as muscles, so I read from a book daily and sprint even if I prefer jogging. What about Swiss habits like all that chocolate?

Dark chocolate after lunch is common, tasty, and rich in polyphenols, and I enjoy the lift. With wine, alcohol alone isn’t healthy, but shared meals and community likely deliver much of the observed benefit in long‑lived cultures.

Moderation and context matter, and the US has a rough food and drinking culture compared to many parts of Europe where meals and drinks center on connection.

Excess is the issue in food or drink; variety and restraint win.

Breathwork may help by steering heart rate and circulation, and many older adults shift to mouth breathing, which could signal poor oxygenation. Let’s test how deliberate breathing patterns change blood chemistry because people can do this at any age and cost.

That study is straightforward by drawing blood before and after; let’s run it.

We need tools beyond the usual loop of sleep, exercise, food, and sunlight—mechanistic readouts for habits.

That’s our aim at Vero: precise, validated advice to make a specific organ biologically younger, based on what actually worked in controlled cohorts. We’re live through a small set of clinics and expanding.

Do you track steps and sleep, and how about measuring light exposure?

I use a watch for steps and sleep and find the data useful. Sunglasses all day concern me because strong daytime light supports mood and circadian health.

More daylight and truly dark evenings improve mental health across very large datasets, though sensitivity to night light varies; bright morning light boxes can help when sunlight is scarce.

Short, foggy Swiss winters made California sun feel like a gift; it makes mornings easier.

What are you most excited about next?

We built proteomic clocks for more than forty human cell types to estimate their biological age; in ALS we see unusually old skeletal and heart muscle cells. In a large cohort with about two decades of follow‑up, that signature at baseline predicted future ALS.

Astrocyte age strongly forecasts Alzheimer’s, especially with genetic risk. We’re also mapping how single‑gene diseases reshape the plasma proteome to create a public atlas that links genes, pathways, and disease patterns.

Your rigor turned a party talking point into real mechanisms, and organ and cell‑type aging measures are a huge step forward; thank you for the work and for sharing it here. I’ll link your papers, and I’ll buy a bottle from your vineyard as a gift for a wine‑drinking friend.

Thank you—this was a pleasure.

Thanks for listening to my conversation with Dr. Tony; see the show notes for resources, and please subscribe on YouTube, follow and review on Spotify and Apple, and support our sponsors.

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