Lifespan with Dr. David Sinclair

At Lifespan, our mission is to help you and your loved ones live your longest, healthiest lives while supporting medical research into breakthroughs to improve all lives. We’re building the world’s largest longevity community: Join us at https://lifespan.com. Follow us on YouTube, Apple, and Spotify for new Lifespan episodes every 2 weeks. __________________________________________ Ozempic and GLP-1s transformed weight loss. Could they also extend lifespan? In this episode, David and Matt look at the emerging science behind that question. They examine a recent study in which semaglutide extended lifespan in female mice, evidence that GLP-1s may influence multiple hallmarks of aging, plus early human research examining biological aging. They also explore how these drugs work, the potential role of the brain, the promise and unanswered questions around microdosing, and what the next generation of GLP-1 therapies could mean for longevity medicine. As David puts it, this class of drugs “might be the world’s first effective longevity medicines."  __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in science and that our team has personally used for years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode - from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat and muscle mass (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan or with code LIFESPAN ○ WHOOP: Get a free WHOOP band and one month of membership at https://join.whoop.com/LIFESPAN or with code LIFESPAN ○ Withings: Get 10% off smart health devices at https://withings.com/lifespan                                __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship.  Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research.   The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

At Lifespan, our mission is to help you and your loved ones live your longest, healthiest lives while supporting medical research into breakthroughs to improve all lives. We’re building the world’s largest longevity community: Join us at https://lifespan.com. Follow us on YouTube, Apple, and Spotify for new Lifespan episodes every 2 weeks.                               __________________________________________ This Lifespan episode explores how what we eat shapes how we age - from inflammation and blood sugar to the trillions of microbes living in our gut. Dr. Sinclair explains how diet affects key biological processes tied to metabolism, health, and longevity. Dr. Sinclair breaks down what sugar does inside the body, including glycation - the process by which sugar attaches to proteins and disrupts their function. The conversation also explores why inflammation rises with age, how the gut microbiome changes over time, and why our ability to sense and respond to nutrients can decline as we get older. Most importantly, Dr. Sinclair explains what we can do about it - from reducing dietary drivers of inflammation and excess sugar to supporting gut health and the nutrient-sensing pathways linked to longevity.  __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in science and that our team has personally used for years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode - from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat and muscle mass (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan or with code LIFESPAN ○ WHOOP: Get a free WHOOP band and one month of membership at https://join.whoop.com/LIFESPAN or with code LIFESPAN ○ Withings: Get 10% off smart health devices at https://withings.com/LIFESPAN                                __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship.  Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research.   The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

At Lifespan, our mission is to help you and your loved ones live your longest, healthiest lives while supporting medical research into breakthroughs to improve all lives. We’re building the world’s largest longevity community: Join us at https://lifespan.com. Follow us on YouTube, Apple, and Spotify for new Lifespan episodes every 2 weeks. __________________________________________ This episode explores why humans are biologically built to move and what happens to the aging process when we don’t. Drawing on evolutionary biology and the latest research, Dr. Sinclair traces physical activity back millions of years, explaining how humans evolved for endurance, why modern sedentary life creates a profound mismatch with our biology, and how exercise activates ancient cellular pathways involved in repair, resilience, metabolism, and longevity. Dr. Sinclair breaks down what happens inside the body when we exercise, including the molecular responses that help us adapt to stress and influence the brain, immune system, metabolism, cardiovascular health, and even the way our cells age. He also tackles some of the biggest questions in exercise science: Can exercise offset sitting all day? Do we compensate for calories burned during exercise? Why did humans evolve such extraordinary endurance? And could exercising with others provide benefits beyond physical fitness? From our evolutionary past to the molecular machinery inside our cells, this episode reveals why movement is so deeply embedded in human biology – and why staying active may be one of the most powerful ways to keep that biology working as we age. __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in science and that our team has personally used for years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode - from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat and muscle mass (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan or with code LIFESPAN ○ WHOOP: Get a free WHOOP band and one month of membership at https://join.whoop.com/LIFESPAN or with code LIFESPAN ○ Withings: Get 10% off smart health devices at https://withings.com/LIFESPAN __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship. Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research. The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

At Lifespan, our mission is to help you and your loved ones live your longest, healthiest lives while supporting medical research into breakthroughs to improve all lives. We’re building the world’s largest longevity community: Join us at https://lifespan.com. Follow us on YouTube, Apple, and Spotify for new Lifespan episodes every 2 weeks.                                __________________________________________ In this episode of Lifespan, Dr. David Sinclair, A.O., Ph.D. – Professor of Genetics at Harvard Medical School and pioneer in longevity research – explores the science of eye aging, vision loss, and emerging strategies to preserve vision throughout life. Dr. Sinclair shares an exclusive update on ER-100, including his team's successful restoration of vision in non-human primates and the launch of the world's first FDA-cleared age reversal human clinical trial. This Phase 1 clinical trial will evaluate the safety of epigenetic cellular restoration as a therapy. Additionally, drawing on decades of research, Dr. Sinclair explains why the eyes may offer one of the earliest windows into biological aging, how everyday factors such as sleep position, alcohol consumption, and intraocular pressure influence long-term eye health, and what the latest evidence reveals about nutrition, supplements, and the connection between the eyes and the brain. Whether you're interested in longevity, brain health, or protecting your eyesight, this episode provides an evidence-based look at the biology of vision and the future of regenerative medicine. 00:00 AI & the First Human Clinical Trial to Reverse Aging 08:30 How the Eye Works 16:00 How Light Sets Your Body Clock 20:18 Your Eyes Are Part of Your Brain 21:34 Can Your Eyes Estimate Your Biological Age? 23:43 Can Eye Exams Help Predict Alzheimer's Disease? 24:43 ER-100: Restoring Vision Through Age Reversal 33:17 Why We Lose Vision as We Age 39:32 How to Keep Your Eyes Healthy as You Age 41:53 The Best Foods & Supplements for Eye Health 49:15 Can Diet & Fasting Protect Your Vision? 53:28 Why Violet Light Matters for Eye Health 59:28 Repairing Eye Damage: UV Light, Smoking & Alcohol 03:45 NASA's Space Mice & Swimming Goggles 05:59 Are You Genetically Predisposed to Eye Disease? 07:48 What's Next in Age Reversal Research?                                __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in science and that our team has personally used for years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode - from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat and muscle mass (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan or with code LIFESPAN ○ WHOOP: Get a free WHOOP band and one month of membership at https://join.whoop.com/LIFESPAN or with code LIFESPAN ○ Withings: Get 10% off smart health devices at https://withings.com/LIFESPAN                                __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship.  Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research.   The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

At Lifespan, our mission is to help you and your loved ones live your longest, healthiest lives while supporting medical research into breakthroughs to improve all lives. We’re building the world’s largest longevity community: Join us at https://lifespan.com. Follow us on YouTube, Apple, and Spotify for new Lifespan episodes every 2 weeks.                               __________________________________________ In this episode of Lifespan Season 2, Dr. David Sinclair, A.O., Ph.D. – Professor of Genetics at Harvard Medical School and pioneer in longevity research – explores the science of calorie restriction and fasting, two of the most studied interventions for healthy aging. Drawing on decades of research, Dr. Sinclair explains how eating less – and eating less often – affects the biology of aging, why our evolutionary past may predispose many of us to weight gain, and what the latest human and animal studies reveal about lifespan, metabolism, and disease risk. Whether you're interested in longevity, metabolism, or intermittent fasting, this episode provides an evidence-based look at one of the most powerful strategies for supporting health and longevity.                                __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in science and that our team has personally used for years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode - from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat and muscle mass (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan or with code LIFESPAN ○ WHOOP: Get a free WHOOP band and one month of membership at https://join.whoop.com/LIFESPAN or with code LIFESPAN ○ Withings: Get 10% off smart health devices at https://withings.com/LIFESPAN                                __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship.  Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research.   The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

What are the most important things you can do today to live longer and stay healthier while doing it? In this final Lifespan Rewind episode, Dr. David Sinclair, A.O., Ph.D., a Professor of Genetics for over 25 years at Harvard Medical School and a leader in the field of longevity research, revisits the most surprising insights from his #1-ranked Season 1 series, combining updated commentary with key moments from across all eight episodes. The result is a thought-provoking, focused, practical guide to the science of longevity – grounded in evidence and designed for real-world application. Whether you're new to longevity science or looking to refine your approach, this episode brings together the most important principles in one place so you can better understand not just what to do, but why it matters. At Lifespan, our mission is to help you and your loved ones live longer, healthier lives while supporting medical research aimed at breakthroughs to extend all our lives. Join us at: https://lifespan.com. We’re building the world’s largest longevity community who will grow, learn, and live longer together. Subscribe here for new Lifespan show episodes every two weeks. __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in strong science – and products our team has personally used for many years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode – from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat content and muscle gains (Withings). If you’d like to learn more or try these tools: ○ Ketone-IQ: Get 30% off your first monthly order at https://ketone.com/lifespan with code LIFESPAN ○. WHOOP: Get a free WHOOP band plus one month free at https://join.whoop.com/LIFESPAN with code LIFESPAN ○. Withings: Explore their smart health devices at https://withings.com/LIFESPAN __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship. Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research. The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

What are the most important things you can do today to live longer and stay healthier while doing it? In this first Lifespan Rewind episode, Dr. David Sinclair, A.O., Ph.D., a Professor of Genetics for over 25 years at Harvard Medical School and a leader in the field of longevity research, revisits the most impactful insights from his #1-ranked Season 1 series, combining updated commentary with key moments from across all eight episodes. The result is a focused, practical guide to the science of longevity – grounded in evidence and designed for real-world application. This episode covers: What to eat – and what to avoid – for long-term health How to think about exercise for longevity (not just performance) The role of cold and heat exposure Which supplements may support healthy aging Emerging medical interventions and what the science actually shows The tools and protocols Dr. Sinclair personally uses in his own routine Whether you're new to longevity science or looking to refine your approach, this episode brings together the most important principles in one place so you can better understand not just what to do, but why it matters. At Lifespan, our mission is to help you and your loved ones live longer, healthier lives while supporting medical research aimed at breakthroughs to extend all our lives. Join us at: https://lifespan.com. We’re building the world’s largest longevity community who will grow, learn, and live longer together.  Subscribe here for new Lifespan show episodes every two weeks.                                __________________________________________ Partners of the Lifespan show help us keep this program freely available as an educational resource while also supporting medical research. We only collaborate with partners whose products are grounded in strong science – and products our team has personally used for many years. Our selected partners make it convenient for the Lifespan audience to access the tools and technologies featured in this episode – from exogenous fuel for neurons (Ketone-IQ), to wearables that track recovery, strain, and sleep (WHOOP), to smart devices that measure key health metrics such as visceral fat content and muscle gains (Withings). If you’d like to learn more or try these tools: Ketone-IQ: Get 30% off your first monthly order at ketone.com/lifespan with code LIFESPAN WHOOP: Get a free WHOOP band plus one month free at join.whoop.com/LIFESPAN with code LIFESPAN Withings: Explore their smart health devices at withings.com/LIFESPAN                                __________________________________________ Legal & Medical Disclaimers The Lifespan show and all related content are provided for informational and educational purposes only and are not intended as medical advice, diagnosis, or treatment. Nothing presented should be interpreted as a recommendation to diagnose, treat, cure, or prevent any disease or medical condition. This content is not a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider. You should always consult with a licensed physician or other qualified healthcare professional before making decisions about your health, including starting, stopping, or modifying any treatment, supplement, diet, or exercise program. The information shared reflects the views and opinions of the host and guests and is based on the scientific literature, their experience and expertise, and general wellness principles. Listening to or engaging with Lifespan content does not establish a doctor–patient or clinical relationship.  Health and longevity outcomes can vary significantly between individuals. Any references to studies, interventions, products, or protocols are not guarantees of specific results, and individual responses may differ. From time to time, Lifespan may discuss or partner with third-party products or services. These references are provided for informational purposes only and should not be considered medical recommendations or endorsements of efficacy for any individual. Lifespan Foundation is an independent 501(c)(3) non-profit organization whose mission is to support medical research.   The views expressed by Dr. David Sinclair, A.O., Ph.D., are his own and do not represent those of Harvard University, Harvard Medical School, or any affiliated institutions.

In this episode of the Lifespan podcast, Dr. David Sinclair and co-host Matthew LaPlante dissect the topic of brain aging. They explore evidence suggesting that the brain ages more slowly than other parts of the body and highlight how cognitive function is impacted by aging. Different interventions aimed at preserving brain health are also discussed, including a plant-based diet, exercise, metformin, NAD boosters, and sufficient sleep. Thank you to our sponsors: Athletic Greens - https://athleticgreens.com/sinclair Levels - https://levels.link/sinclair InsideTracker - https://insidetracker.com/sinclair Our Patreon page: https://www.patreon.com/davidsinclair Lifespan book: https://amzn.to/3sUqurT Dr. David Sinclair Social: Instagram Twitter Facebook Matthew LaPlante's Social: Twitter To stay up to date with David's work to democratize biological age testing and insights, visit tallyhealth.com. Timestamps: (00:00:00) Introducing Episode Seven: Aging of the Brain (00:04:39) Thanking the Sponsors (00:07:38) Ex-differentiation as a Driver of Aging (00:09:22) The Brain Ages Slowly (00:14:17) Cognitive Function and Plasticity (00:17:44) Three Longevity Pathways: mTOR, AMPK, and Sirtuins (00:23:26) Plant-based Diets and B-vitamins (00:28:32) Homocysteine, Plaque, and Vasculature (00:32:35) Fatty Acids (00:35:48) Physical Activity (00:39:14) Metformin (00:46:02) NAD Boosters (00:50:33) Increasing Blood Flor (00:53:20) Sleep (00:58:02) Overall Message: Keep your Brain Healthy (00:58:50) Next Week’s Episode and the Future of Medicine (01:01:21) Options for Subscription for Support For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

In this week’s episode of the Lifespan podcast, Dr. David Sinclair and co-host Matthew LaPlante cover potential anti-aging interventions that are on the cutting edge. They share the latest research surrounding testosterone replacement therapy (TRT), human growth hormone (HGH), peptide supplementation, exosomes, stem cells, and cellular reprogramming. The idea of human rejuvenation and potential paths towards resetting the aging clock is also discussed. Thank you to our sponsors: Athletic Greens - https://athleticgreens.com/sinclair InsideTracker - https://insidetracker.com/sinclair Levels - https://levels.link/sinclair Our Patreon page: https://www.patreon.com/davidsinclair Lifespan book: https://amzn.to/3sUqurT Dr. David Sinclair Social: Instagram Twitter Facebook To stay up to date with David's work to democratize biological age testing and insights, visit tallyhealth.com. Matthew LaPlante's Social: Twitter Timestamps: (00:00:00) Kicking Off Episode Five: Interventions on the Cutting Edge (00:02:39) Expressing Gratitude to the Sponsors (00:05:28) Testosterone Replacement Therapy (00:10:09) Human Growth Hormone (00:13:56) Peptide Supplementation and Regenerative Signaling (00:18:11) MOTS-c, Humanin, and Other Peptides (00:25:05) Exosome Therapy (00:31:56) A Primer on Stem Cells and Yamanaka Factors (00:37:59) Stem Cell Aging and Cord Blood Banking (00:41:42) The Therapeutic Potential of Stem Cells (00:43:37) Cellular Reprogramming (00:51:35) Resetting the Aging Clock (00:56:50) The Future Looks Bright (00:58:15) Next Week’s Episode: External Aging (00:58:36) Subscription and Support Options For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

In Episode 3 of the Lifespan Podcast, Dr. David Sinclair and Matthew LaPlante dive deeply into the science of non-dietary interventions that mimic adversity and promote health. They begin by highlighting how different types of physical activity (i.e., low-intensity aerobic exercise, high-intensity aerobic exercise, and weight training) protect against age-related disease and enhance longevity. David and Matthew additionally highlight the latest evidence behind hyperbaric oxygen therapy, cold therapy, and heat therapy. As they discuss different adversity mimetics, they also explain how these interventions influence aging at the molecular and physiological levels. Thank you to our sponsors: Athletic Greens - https://athleticgreens.com/sinclair Levels - https://levels.link/sinclair InsideTracker - https://insidetracker.com/sinclair Our Patreon page: https://www.patreon.com/davidsinclair Timestamps: (00:00:00) Introducing Episode 3: Exercise Hot Cold (00:01:01) A Pernicisous Element Called Iron (00:02:46) A Quick Primer on Free Radicals (00:05:42) Review of Dietary Takeaways (00:07:01) Sponsors (00:09:32 Biological Adversity & the Survival Circuit (00:13:24) Survival Sensors (i.e., mTOR, AMPK, and Sirtuins) & Communicators (e.g., Insulin) (00:17:25) Get Off Your Butt (00:19:40) Exercise Protects against Disease & Mortality (00:21:17) Daily Step Count and Walking After Eating (00:22:33) Exercise Activates AMPK and Creates More Mitochondria (00:24:03) Vigorous Exercise, Hypoxia, the Electron Transport Chain (00:28:19) Exercise Increases Glucose Sensitivity and Stimulates Blood Vessel Formation (00:32:13) The Epigenome and Biological Age are Impacted by Exercise (00:36:43) How to Measure your Biological Age (00:37:31) Exercise Recommendations (00:39:28) Wearables and Individualized Health Tracking (00:43:14) The Importance of Weight Training (00:46:08) Physical Activity & Senescent Cells (00:48:01) Wrap-up & Takeaways (00:49:47) Hyperbaric Oxygen Therapy (00:57:24) Cold Therapy (01:03:50) Applying Heat (01:07:04) Adversity Mimetics Produce Endorphins (01:08:07) A Basic Protocol for Mimicking Adversity (01:10:04) Next Week: Molecules & Supplements (01:10:45) Subscription & Support For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.

In this episode, Dr. David Sinclair and co-host Matthew LaPlante discuss why we age. In doing so, they discuss organisms that have extreme longevity, the genes that control aging (mTOR, AMPK, Sirtuins), the role of sirtuin proteins as epigenetic regulators of aging, the process of "ex-differentiation" in which cells begin to lose their identity, and how all of this makes up the "Information Theory of Aging", and the difference between "biological age" and "chronological age" and how we can measure biological age through DNA methylation clocks. Thank you to our sponsors: Athletic Greens - https://athleticgreens.com/sinclair InsideTracker - https://insidetracker.com/sinclair Levels - https://levels.link/sinclair Our Patreon page: https://www.patreon.com/davidsinclair Lifespan book: https://amzn.to/3sUqurT Dr. David Sinclair Social: Instagram Twitter Facebook To stay up to date with David's work to democratize biological age testing and insights, visit tallyhealth.com. Matthew LaPlante's Social: Twitter Timestamps: (00:00:00) Introduction (00:03:14) Goal of the Lifespan Podcast (00:07:11) Acknowledgement of Sponsors (00:10:45) Aging is a Controllable Process that can be Slowed & Reversed (00:16:42) Organisms with Extreme Longevity (00:21:47) Genes that Regulate Aging: mTOR, AMPK, Sirtuins (00:21:55) mTOR & Rapamycin (00:24:33) AMP-activated protein kinase (AMPK) & Metformin (00:30:57) Sirtuin Proteins as Epigenetic Regulators of Aging (00:35:33) Ex-Differentiation (00:43:30) Measuring Aging - Biological Age vs. Chronological Age (00:49:30) "No Law That Says We Have To Age" (00:50:33) Episode Summary & Key Takeaways - Why Do We Age? (00:54:00) Information Theory of Aging (00:57:59) Aging is a Medical Condition (01:01:00) Aging Myths - Telomeres & Antioxidants (01:01:55) Options for Subscription and Support For the full show notes, including the peer-reviewed studies, visit the Lifespan podcast website. Please note that Lifespan with Dr. David Sinclair is distinct from Dr. Sinclair's teaching and research roles at Harvard Medical School. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Lifespan with Dr. David Sinclair podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. Special thanks to our research assistants, Adiv Johnson & Sarah Ryan.