Restoring Youthfulness & Vitality to the Aging Brain & Body: Bloodborne Factors and Organ-Specific Aging with Dr. Tony Wyss-Coray

This episode features Dr. Tony Wyss-Coray, a pioneer in the science of aging and rejuvenation, discussing his groundbreaking work on how factors in young blood can reverse aspects of aging in older organisms. He details the parabiosis experiments in mice, where the circulatory systems of young and old mice are joined, leading to the reactivation of stem cells, reduced inflammation, increased brain activity, and improved memory function in the older animals. This work highlights that bloodborne factors are not merely indicators of health but active agents capable of influencing cellular and organ function, with their composition changing dramatically from youth to old age.

The discussion then transitions to the translation of these findings to humans. Dr. Wyss-Coray's company, Alkahest, demonstrated that young human blood could mimic the rejuvenating effects seen with young mouse blood in mouse brains. Collaborations with Grifols, a company producing plasma-derived medicines, led to clinical trials in Alzheimer's and Parkinson's patients using specific plasma fractions, showing promising results. The concept of therapeutic plasma exchange (plasmapheresis), where plasma is removed and replaced, is also explored, with a 500-patient Grifols study showing significant benefits in Alzheimer's patients, and a smaller trial by Circulate Therapeutics indicating that this process could make organs appear younger according to epigenetic clocks.

A crucial insight from Dr. Wyss-Coray's research is that aging is not a uniform, linear process across the entire organism. Different organs and even cells within an organism age at varying rates. His lab has developed molecular tools to measure thousands of proteins in a drop of blood, identifying organ-specific proteins that change with age. This allows for the estimation of an individual's 'organ age' (e.g., liver age, heart age, brain age). The 'age gap'—the difference between chronological age and estimated organ age—is a powerful predictor of future disease risk in that specific organ, offering a personalized approach to health.

Building on this, Dr. Wyss-Coray co-founded Vero Biosciences, aiming to profile organ age to predict and ideally eradicate chronic diseases. Their 'Vero Compass' platform combines biological signatures with clinical and wearable data to identify which organs are most sensitive to aging, suggest tailored interventions (medical treatments, lifestyle changes like diet and exercise), and then monitor the effectiveness of these interventions through repeated testing. This personalized approach could revolutionize drug development by targeting specific disease profiles, potentially rescuing effective treatments that failed in broad clinical trials due to patient heterogeneity or late-stage application. The episode also briefly touches on other longevity factors like sunlight, fasting, hormones, and the historical context of blood-related lore.

"for the first time we could take an old brain and we could give factors from a young organism and ask is that going to change the age of the brain and that's indeed what it did."

"there are factors in the blood that clearly can change the function of cells and organs."

"The composition changes dramatically from young to old. We have this picture that I always like to show when I give a a talk about our work where we have um several thousand individuals and we measure 3,000 proteins in them and then we use collars to show low levels or high levels of proteins and you see this dramatic change from young people to old people in a way that you can pick one sample and you can say this person must be about that old."

"So what we see is with age there's an increase in many what we call inflammatory proteins and we actually identified some and in mice if we knock them out or if we neutralize them then cognition improves in the mice in old mice."

"our blood is nature's cocktail, right? It's the the alexia of youth. It just sort of or it's the fountain of youth that lives in us, but it dries out as we get older."

"what we clearly see is that organs and cells within uh an organism can have slightly different rates of aging."

"The way how we make this what people call a clock for a specific organ is we look in your blood for proteins for example from the brain... And that allows us to then estimate the age of the liver in an individual."

"if your heart shows to age faster, you're more likely to get heart disease or a heart attack. If your kidney ages fast, you're going to get kidney disease. If your brain ages faster, you're more likely going to get Alzheimer's disease."

"The Vero Compass uses a combination of this biological signature together with clinical and wearable data to create a platform that can predict how you respond, which or first of all which organ is the most sensitive, which intervention you can use and then whether your organ responds or not by repeated testing and sort of creating a continuous loop where I tell you which organ is of concern."

"I think we may have tested a lot of drugs out there that might actually be beneficial, but because we apply them to everyone and we apply them too late, they fail and we throw them away."