Longevity roundtable — the science of aging, geroprotective molecules, lifestyle interventions, challenges in research, and more | Steven Austad, Matt Kaeberlein, Richard Miller

Peter Attia

Jan 27, 2025

Episode description

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In this special episode of The Drive, Peter introduces a brand-new roundtable format. Joined by three renowned experts in longevity science—Steven Austad, Richard Miller, and Matt Kaeberlein—the group explores the rapidly evolving field of geroscience. Together, they dive deep into topics like the relationship between healthspan and lifespan, evaluating interventions like rapamycin and senolytics, the role of epigenetic changes in aging, and whether GLP-1 receptor agonists hold geroprotective potential. They also tackle major challenges in funding and public acceptance of longevity research including how geroprotective interventions might be tested in humans. Packed with nuanced debate, humor, and groundbreaking insights, this episode is a must-listen for anyone fascinated by the science of aging.

We discuss:

  • The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan [3:45];

  • Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype [12:30];

  • The need to redirect medical research from disease-specific models to aging-focused approaches [21:30];

  • Proactive healthcare: rethinking health, disease, and the role of aging [30:00];

  • Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks [35:00];

  • The utility and drawbacks of the “hallmarks of aging” as a framework for research and funding [49:30];

  • The role of epigenetic changes in aging and the challenges of proving causality [56:45];

  • The translational challenges of moving aging research from preclinical studies to human applications [1:03:45];

  • Distinguishing between a biomarker of aging and aging rate indicators [1:17:15];

  • The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans [1:21:15];

  • Exercise, aging, and healthspan: does exercise slow aging? [1:35:45];

  • Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects? [1:41:00];

  • The role of senescent cells in aging, challenges with reproducibility in studies, and differing view

Episode description

View the Show Notes Page for This Episode

Become a Member to Receive Exclusive Content

Sign Up to Receive Peter’s Weekly Newsletter

In this special episode of The Drive, Peter introduces a brand-new roundtable format. Joined by three renowned experts in longevity science—Steven Austad, Richard Miller, and Matt Kaeberlein—the group explores the rapidly evolving field of geroscience. Together, they dive deep into topics like the relationship between healthspan and lifespan, evaluating interventions like rapamycin and senolytics, the role of epigenetic changes in aging, and whether GLP-1 receptor agonists hold geroprotective potential. They also tackle major challenges in funding and public acceptance of longevity research including how geroprotective interventions might be tested in humans. Packed with nuanced debate, humor, and groundbreaking insights, this episode is a must-listen for anyone fascinated by the science of aging.

We discuss:

  • The recent rise in public interest in longevity, misconceptions, and the link between healthspan and lifespan [3:45];

  • Redefining healthspan, the US healthcare paradox, and separating longevity science from commercial hype [12:30];

  • The need to redirect medical research from disease-specific models to aging-focused approaches [21:30];

  • Proactive healthcare: rethinking health, disease, and the role of aging [30:00];

  • Biologic age versus chronologic age, and the limitations and potential of epigenetic clocks [35:00];

  • The utility and drawbacks of the “hallmarks of aging” as a framework for research and funding [49:30];

  • The role of epigenetic changes in aging and the challenges of proving causality [56:45];

  • The translational challenges of moving aging research from preclinical studies to human applications [1:03:45];

  • Distinguishing between a biomarker of aging and aging rate indicators [1:17:15];

  • The difficulties of translating longevity research in mice to humans, and the difficulties of testing interventions in humans [1:21:15];

  • Exercise, aging, and healthspan: does exercise slow aging? [1:35:45];

  • Are GLP-1 receptor agonists geroprotective beyond caloric restriction effects? [1:41:00];

  • The role of senescent cells in aging, challenges with reproducibility in studies, and differing view

Mindsip insights from this episode:

Reevaluate cellular senescence research based on flawed origins

The entire field of cellular senescence may be a "terrible historical accident" based on a joke, with a specific senolytic drug, Fisetin, showing no effect on lifespan or senescent cells in ITP mice.

Reject trade-off myth: healthspan and lifespan are interconnected

Interventions that extend lifespan in mice do so by postponing diseases, making the idea of a trade-off between healthspan and lifespan a ridiculous and false metaphor.

Reevaluate the concept of healthspan for clarity

The term "healthspan" is considered vacuous and nebulous because it's impossible to define with a single number when a person's health has officially ended.

Challenge turf wars to secure aging research funding

The NIH is unlikely to properly fund aging research because disease-specific fields like cardiology and oncology view it as an invasion and defend their budgets with a "porcupine defense.".

Question the reliability of biological age kits due to inconsistent results

A self-experiment on four direct-to-consumer epigenetic age kits yielded a 21-year range in biological age from the same sample, suggesting the industry is a "complete mess.".

Challenge the limitations of "hallmarks of aging" to advance research

The famous "Hallmarks of Aging" may have set the field back by creating an arbitrary list that stifles research on unlisted topics and allows researchers to avoid proving their work's importance.

Implement aging rate indicators to test anti-aging drugs effectively

To effectively test anti-aging drugs in humans, we need "aging rate indicators" (like a speedometer) that measure the rate of aging, not just biomarkers (like an odometer) that measure the state of aging.

Debunk resveratrol myths: lifespan extension not proven

The only study showing resveratrol extended mouse lifespan was in mice fed a toxic diet that caused fatal liver expansion, and the drug merely prevented this specific pathology, not aging itself.

Question NAD precursors' value over inexpensive niacin

Data suggests that expensive NAD precursors like NMN and NR are broken down into simple niacin in the gut, questioning their value over a much cheaper alternative.

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