Anti-Aging Scientist: What To Eat & When To Eat To Slow The Aging Process | Matt Kaeberlein
Matt Kaeberlein, an aging biology expert, discusses the science of anti-aging with host Tom Bilyeu, covering caloric restriction, rapamycin, epigenetic clocks, and the Dog Aging Project. He emphasizes that aging interventions are not one-size-fits-all and cautions against overstated claims about reversing aging, while presenting evidence that rapamycin shows promise for extending healthspan in both mice and dogs.
Summary
Matt Kaeberlein, a professor of pathology and founder of the Dog Aging Project, joins Tom Bilyeu to explore the science behind aging and longevity interventions. The conversation begins with a critical examination of caloric restriction, long considered the most robust lifespan-extending intervention in laboratory animals. Kaeberlein explains that while caloric restriction can increase lifespan by up to 60% in mice, this effect varies dramatically by genetic background—approximately one-third of genetically distinct mouse lines show no benefit or actually experience shortened lifespans from caloric restriction. He emphasizes that humans are genetically diverse like these mice, and there are also significant psychological and behavioral challenges to maintaining caloric restriction that aren't present in controlled laboratory settings. Tom shares his personal experience with 25% caloric restriction, describing it as psychologically damaging and noting that it attracted criticism from loved ones about his personality changes.
The discussion moves to broader nutritional principles beyond simple caloric restriction. Kaeberlein advocates for healthy whole foods diets with reduced ultra-processed foods, but resists prescribing one-size-fits-all nutritional frameworks. He discusses his own preference for a low-carbohydrate diet while acknowledging it may not work for everyone. The conversation highlights the tension between needing actionable guidelines for the general population (who are currently worse off than optimal) versus acknowledging that optimal nutrition is highly individual and requires personal experimentation and biomarker tracking.
A significant portion of the interview focuses on rapamycin (sirolimus), an mTOR inhibitor that Kaeberlein presents as the second most effective lifespan-extending intervention after caloric restriction in laboratory animals. Unlike caloric restriction, rapamycin can be administered starting in middle age and still produce substantial benefits, which has major implications for human application. Kaeberlein discusses preliminary results from the Dog Aging Project's rapamycin trials, showing evidence of reversed age-related heart decline, increased activity in older dogs, and potentially protective effects against viral infections including COVID-19. He notes that unpublished survey data from 333 people taking rapamycin off-label found minimal serious side effects, with mouth sores in about 10% of users and approximately twofold increased bacterial infection risk—a small risk given the potential benefits.
The conversation addresses the problem with current biological aging clocks, particularly epigenetic clocks that have gained commercial popularity. Kaeberlein raises a critical concern that these clocks may primarily be measuring immune cell composition in blood rather than true biological age, potentially showing rapid apparent "aging reversal" that is actually just immune system remodeling. He explains that changes in immune cell populations can occur quickly (from infections or other stimuli) and might be misinterpreted as aging changes. This caveat is important given claims by some biohackers of reversing their epigenetic age by years in just months.
The interview explores the nine hallmarks of aging and their interconnections, with Kaeberlein emphasizing that we still don't understand whether there's a single underlying principle driving all hallmarks or whether they represent a network of independent processes. He notes that mTOR appears to be a particularly important node in this network—tweaking it has outsized effects on lifespan and healthspan across multiple species from yeast to mice. The conversation addresses whether inflammation is the fundamental driver of aging, with Kaeberlein explaining that while mTOR inhibition does reduce sterile inflammation, the fact that rapamycin works in yeast (which lack immune systems) suggests inflammation is likely a downstream effect rather than the root cause.
Kaeberlein discusses obesity as an accelerating factor in aging, explaining that adipose tissue itself produces inflammatory signals, but also that obesity increases metabolic demands on organs like the liver and kidneys. The conversation addresses whether the benefits of caloric restriction come from the caloric restriction itself or simply from avoiding obesity—an important distinction he notes can't yet be definitively answered. He also discusses the microbiome's role in weight regulation and food cravings, and mentions ongoing research into whether the hypothalamic set point for body fat can be adjusted.
The interview concludes with practical advice for someone attempting to optimize for longevity. Kaeberlein recommends comprehensive biomarker tracking including standard clinical panels (lipid profiles, glucose markers), comprehensive hormonal panels, and exploratory high-dimensional measures like proteomics and metabolomics. He expresses skepticism about current epigenetic clocks' predictive value while recognizing their potential as we gain more data. He advocates for hormone replacement therapy when clinically appropriate, noting it has gotten an unfair bad reputation. The discussion returns to the measure-intervene-measure-again approach, emphasizing that personalized optimization requires tracking responses over time since we cannot yet predict individual responses to interventions.
About this episode
<p>You just want to look better, feel better, have bigger muscles, tighter skin, and a sexier body you can enjoy and be proud of. The information and narratives floating around on how to achieve that are all over the place, and understanding how to discern what the takeaway action is going to be for you to achieve results is really what you need.</p><p>Matt Kaeberlein, Director of the Biological Mechanisms of Healthy Aging Training Program, and founder and co-Director of the Dog Aging Project, is a biologist best known for his research on evolutionarily conserved mechanisms of aging.</p><p>When you’re doing your own research into what things you can be doing to optimize your health and lifespan, Matt warns that you’ll need to be careful of research studies with narratives that lean one-sided.</p><p>Some of the key ideas Matt and Tom discuss in this episode around anti-aging that will perk up your ears are:</p><p>Why Matt calls BS on “Reverse-Aging”</p><p>What the drug Rapamycin has the potential to do for long term health</p><p>What metrics should we be measuring for good health and anti-aging</p><p>With all the years of experience from Matt Kaeberlein as a biologist specializing in anti-aging, he confirms that exercise and nutrition are as effective as exogenous drugs such as Rapamycin.</p><p>Are we busy trying to create complicated solutions to anti-aging, longevity and health that plain old boring nutrition and exercise can take care of already?</p><p>Check out Matt Kaeberlein’s Dog Aging Project: https://dogagingproject.org/</p><p><br /></p><p><strong>QUOTES:</strong></p><p>“We know things like rapamycin, [...] can reverse some of the functional declines that go along with aging.”</p><p>“I’m not so sure that exercise and nutrition are fundamentally different from rapamycin. Exercise hits the hallmarks of aging, it affects biological aging.”</p><p><br /></p><p><strong>Follow Matt Kaeberlein:</strong></p><p>Website: https://kaeberlein.org/</p><p>Twitter: https://twitter.com/mkaeberlein</p><p>Instagram: https://www.instagram.com/dogagingproject/</p><p><br /></p><p>SPONSORS:</p><p>Get 5 free AG1 Travel Packs and a FREE 1 year supply of Vitamin D with your first purchase at <a href="https://bit.ly/AG1Impact" target="_blank">https://bit.ly/AG1Impact</a>.</p><p>Sign up for a one-dollar-per-month trial period at <a href="https://bit.ly/ShopifyImpact" target="_blank">https://bit.ly/ShopifyImpact</a> and supercharge your business!</p><p>Get FREE GROUND BEEF FOR LIFE plus $20 off your first box at <a href="https://bit.ly/ButcherBoxImpact" target="_blank">https://bit.ly/ButcherBoxImpact</a>.</p><p>Get 55% off at <a href="https://bit.ly/BabbelImpact" target="_blank">https://bit.ly/BabbelImpact</a> and learn a new language today!</p><p><br /></p><p><strong><em>Are You Ready for EXTRA Impact?</em></strong></p><p>If you’re ready to find true fulfillment, strengthen your focus, and ignite your true potential, the Impact Theory subscription was created just for you.</p><p>This is not for the faint of heart. This is for those who dare to learn obsessively, every day, day after day.</p><p><strong>Subscription Benefits:</strong></p><ul> <li>Unlock the gates to a treasure trove of wisdom from inspiring guests like Andrew Huberman, Mel Robbins, Hal Elrod, Matthew McConaughey, and many, many, more</li> <li>New episodes delivered ad-free</li> <li>Exclusive access to Tom’s AMAs, keynote speeches, and suggestions from his personal reading list</li> <li>You’ll also get access to an<strong> <em>5 additional podcasts</em> </strong>with hundreds of archived Impact Theory episodes, meticulously curated into themed playlists covering health, mindset, business, relationships, and more:</li> <li> <a href="https://podcasts.apple.com/us/podcast/legendary-mindset/id1683397827?itsct=podcast_box&itscg=30200&ls=1&at=1000l3anZ" target="_blank"><strong>Legendary Mindset</strong></a><strong>:</strong> Mindset & Self-Improvement</li> <li> <a href="https://podcasts.apple.com/us/podcast/money-mindset/id1683397173?itsct=podcast_box&itscg=30200&ls=1&at=1000l3anZ" target="_blank"><strong>Money Mindset</strong></a><strong>: </strong>Business & Finance</li> <li> <a href="https://podcasts.apple.com/us/podcast/relationship-theory/id1683229040?itsct=podcast_box&itscg=30200&ls=1&at=1000l3anZ" target="_blank"><strong>Relationship Theory:</strong></a> Relationships</li> <li> <a href="https://podcasts.apple.com/us/podcast/health-theory/id1683215287?itsct=podcast_box&itscg=30200&ls=1&at=1000l3anZ" target="_blank"><strong>Health Theory</strong></a><strong>: </strong>Mental & Physical Health</li> <li> <a href="https://podcasts.apple.com/us/podcast/power-ups/id1683398038?itsct=podcast_box&itscg=30200&ls=1&at=1000l3anZ" target="_blank"><strong>Power Ups:</strong></a> Weekly Doses of Short Motivational Quotes </li> </ul><p><br /></p><p>Subscribe on Apple Podcasts: <a href="https://apple.co/3PCvJaz" target="_blank">https://apple.co/3PCvJaz</a></p><p>Subscribe on all other platforms (Google Podcasts, Spotify, Castro, Downcast, Overcast, Pocket Casts, Podcast Addict, Podcast Republic, Podkicker, and more) : <a href="https://impacttheorynetwork.supercast.com/" target="_blank">https://impacttheorynetwork.supercast.com/</a></p><p> </p><p>Learn more about your ad choices. Visit <a href="https://megaphone.fm/adchoices" target="_blank">megaphone.fm/adchoices</a></p><p>See Privacy Policy at <a href="https://art19.com/privacy" rel="noopener noreferrer" target="_blank">https://art19.com/privacy</a> and California Privacy Notice at <a href="https://art19.com/privacy#do-not-sell-my-info" rel="noopener noreferrer" target="_blank">https://art19.com/privacy#do-not-sell-my-info</a>.</p>
Key Insights
- Kaeberlein reports that in 41 different genetically inbred mouse lines, approximately one-third showed significant lifespan extension from caloric restriction, another third showed no effect, and 25-33% actually experienced shortened lifespans from the same intervention.
- Kaeberlein explains that rapamycin can extend lifespan and reverse age-related functional decline when started in middle age (mouse equivalent of age 60), unlike most aging interventions that require early-life administration.
- Kaeberlein argues that current epigenetic aging clocks may primarily measure immune cell composition in blood rather than true biological age, potentially explaining claims of rapid aging reversal that are actually immune system remodeling.
- Kaeberlein states that rapamycin works in yeast (which lack immune systems) and simple organisms with rudimentary immunity, suggesting inflammation is likely a downstream consequence of mTOR hyperactivation rather than the fundamental driver of aging.
- Kaeberlein presents unpublished data from 333 people taking rapamycin off-label showing approximately twofold increased bacterial infection risk but minimal serious side effects, with mouth sores in about 10% of users.
- Kaeberlein reports preliminary Dog Aging Project results showing evidence of reversed age-related heart decline in the left ventricle and increased activity levels in older dogs given rapamycin.
- Kaeberlein notes that rapamycin appears to enhance resistance to viral infections through upregulation of antiviral gene expression, and unpublished data suggests people taking rapamycin continuously had much lower risk of severe COVID-19 infection or long COVID.
- Kaeberlein argues that we cannot yet definitively determine whether benefits of caloric restriction come from the restriction itself or simply from avoiding obesity, as studies cannot easily separate these variables.
- Kaeberlein explains that the magnitude of lifespan extension from simple interventions like caloric restriction decreases in longer-lived organisms, with smaller effects observed as you move from yeast to worms to flies to mice.
- Kaeberlein contends that biological aging is primarily an absence of evolutionary selection rather than a programmed process, since natural selection doesn't favor traits that extend lifespan after reproductive years.
- Kaeberlein states that hundreds of genes have been identified that increase lifespan when mutated in simple organisms, but most have not been studied because researchers focus on genes affecting conserved pathways across species.
- Kaeberlein argues against the concept of 'age reversal,' stating there is no evidence that any organism has been made biologically young again, and that the term gets misused in popular discussions of aging interventions.
Topics
Transcript
You're listening to this podcast, so I know you've got a curious mind. Here's a helpful fact you might not know yet. Drivers who switch and save with Progressive save over $900 on average. Pop over to Progressive.com, answer some questions, and you'll get a quick quote with discounts that are easy to come by. In fact, 99% of their auto customers earn at least one discount. Visit Progressive.com and see if you can enjoy a little cash back. Progressive Casualty Insurance Company and Affiliates. National average 12-month savings of $946 by new customers surveyed who saved with Progressive between June 2024 and May 2025. Potential savings will vary. Why does Progressive work hard for truckers? Because truckers unite the…
Full transcript available for MurmurCast members
Sign Up to AccessMore from Tom Bilyeu's Impact Theory
What Broke The Bond Market — And Why They're Going To Print Your Savings Away
Felix discusses the breaking bond market driven by unsustainable US government debt spending, explaining that inflation through money printing is the inevitable outcome rather than fiscal responsibility. He outlines how this mirrors Japan's lost decades and provides strategies for individual investors to protect themselves through diversification and understanding money flows.
Japan’s $35 Trillion Meltdown, US Debt Nightmare & The AI Lifeline | Tom Bilyeu Show
Tom Bilyeu discusses geopolitical tensions between Russia, China, Iran, and the US, the destabilization of global markets through Japan's economic crisis and the yen carry trade unwinding, and the need for America to pursue AI-driven growth while maintaining law and order domestically. He emphasizes that cultural and economic alignment around growth, merit, and strength is essential for navigating these interconnected global crises.
The Dollar's Last Stand: Scott Bessent's $950 Billion Plan to Save the Bond Market
The transcript explores how the U.S. dollar's status as the world's reserve currency functions as a resource curse, examining Treasury Secretary Scott Bessent's strategy to manage the bond market crisis through shifting debt from long-term to short-term instruments backed by cryptocurrency stablecoins, while J.D. Vance questions whether reserve currency status actually benefits America.
Weapon-Grade AI, China’s Power Move & Why the Middle Class Is at Risk | Tom Bilyeu Show
Tom Bilyeu discusses weaponized AI capabilities, the Iran conflict and military munitions depletion, China's geopolitical strategy, and a growing loneliness epidemic particularly affecting women—all stemming from broken social structures and evolutionary mismatches with modern life.
Bessent Breaks the Bond Market, The China Pivot That Could Sink Canada's Economy, Kisin vs Keen | Weekly Recap
The episode covers debates on climate innovation versus degrowth, Treasury Secretary Bessent's bond market interventions and their limitations, and Canada's failed trade negotiations with the US while pivoting toward China—highlighting broader themes of deglobalization, currency instability, and the necessity of real economic growth to avoid systemic collapse.