
Rapamycin, NAD & the Truth About Slowing Aging | Matt Kaeberlein
What if the most promising drug for slowing aging already exists.. but we still do not know whether healthy humans should take it? Dr. Matt Kaeberlein is one of the leading scientists studying the biology of aging. His work has focused on mTOR, rapamycin, cellular aging and the mechanisms that may allow us to extend healthy lifespan. In this episode of Return on Health, hosts Niko Hems and Miguel Medina challenge Matt on how far longevity science has actually come. They discuss what aging really is, whether the Hallmarks of Aging are causes or consequences, and why changing one pathway or biomarker often fails to produce the health outcome we expect. The conversation then turns to rapamycin. Matt explains why it has some of the strongest preclinical evidence of any potential longevity intervention, why it has extended lifespan across multiple animal models, what decades of use in transplant medicine tell us about safety, and why the doses used for longevity are very different. They also discuss the biggest unanswered question: does any of this translate meaningfully to healthy humans? Matt explains why he personally uses rapamycin periodically, what he thinks about emerging evidence in chronic inflammation and ME/CFS, and why its effects on mTOR do not necessarily mean it will accelerate age-related muscle loss. The episode also takes on some of the biggest claims in longevity. Matt argues that the human evidence behind NAD supplementation remains weak, warns against stacking large numbers of supplements with uncertain effects, and explains why many consumer-facing biological age tests are currently far less useful than their marketing suggests. They also discuss longevity escape velocity, whether AI could accelerate aging research, rapamycin vs GLP-1 receptor agonists vs metformin, and why companion dogs may be one of the most useful models for understanding human aging. ━━━━ 👤 ABOUT THE GUEST ━━━━ Matt Kaeberlein, PhD is a scientist focused on the biological mechanisms of aging and interventions that may extend healthspan. His research has covered mTOR signaling, rapamycin, cellular aging and lifespan regulation. He is also a co-founder of the Dog Aging Project, which studies how genetics, environment and interventions influence aging in companion dogs. ━━━━ 🎙️ ABOUT THE HOSTS ━━━━ Niko Hems is Head of Strategy & Medical Communications at YEARS, a preventive medicine company using longitudinal and multi-modal health data to make prevention more personalized and data-driven. Miguel Medina is co-host of Return on Health, a podcast built around a simple idea: a system produces the outcomes it is incentivized to produce — so better health outcomes require better incentives. ━━━━ 💡 KEY QUESTIONS ANSWERED ━━━━ • What actually causes biological aging? • Are the Hallmarks of Aging incomplete? • Why is mTOR so important for longevity? • Can rapamycin really slow aging? • How strong is the human evidence? • What are the main risks and side effects? • Does rapamycin interfere with muscle growth? • Could it help with chronic inflammation or ME/CFS? • Is there strong evidence for NAD supplements? • Are biological age tests useful yet? • Is longevity escape velocity scientifically realistic? • Rapamycin vs GLP-1s vs metformin: where is the strongest evidence? • Why could studying dogs help us understand human aging? ━━━━━━━━━━━━━━━ Connect with Matt: Dog Aging Project: https://dogagingproject.org/








