Modern Healthspan

Discover how the "Brain Energy Gap" drives cognitive decline and how ketones can rescue starving neurons. Dr. Stephen Cunnane explains the science of metabolic health, the BENEFIC trial, and how to fuel a hybrid brain for long-term longevity.

Is Alzheimer’s actually a fuel shortage in the brain? In this interview, world-renowned researcher Dr. Stephen Cunnane breaks down the "Brain Energy Gap", a critical metabolic deficit where the brain loses its ability to utilize glucose efficiently as we age. While this energy gap can lead to Mild Cognitive Impairment (MCI) and Alzheimer’s, Dr. Cunnane’s groundbreaking research, including the landmark BENEFIC trial, shows that ketones can bypass this blockage to provide a vital backup fuel source.

We dive deep into the hybrid brain concept, exploring how Medium Chain Triglycerides (MCTs) and specific dietary shifts can "rescue" cognitive function by doubling brain ketone uptake. Dr. Cunnane also discusses the "double jeopardy" of insulin resistance and why managing metabolic health is the most promising frontier for preventing neurodegeneration. Whether you are interested in brain health, longevity, or the clinical applications of ketogenic metabolic therapy, this technical deep dive offers essential insights into the future of healthy aging

🌐Links in this video

A ketogenic drink improves cognition in mild cognitive impairment: Results of a 6‐month RCT https://pmc.ncbi.nlm.nih.gov/articles/PMC8048678/ Improved brain energetics and cognition after a 6-month ketogenic intervention in mild cognitive impairment: Final results of the Benefic Trial https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1002/alz.037961 A reduced carbohydrate diet improves glycemic regulation in hyperglycemic older people in a retirement home: the SAGE study https://cdnsciencepub.com/doi/10.1139/apnm-2024-0277

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Muscle scientist Dr Brad Schoenfeld on how to stay strong after 60.

Dr Brad Schoenfeld is a professor of exercise science at Lehman College, New York, and one of the world's most cited researchers on muscle hypertrophy. In this interview we cover the practical science of building and maintaining muscle as you age with a focus on what actually matters for healthspan and independence.

We discuss how much training older adults really need, why power matters more than strength for fall prevention, and how to think about loads and reps after 60. Brad also explains why protein requirements increase with age, what the leucine threshold is and why it matters, and gives his frank assessment of the supplement landscape including the one he thinks has genuine evidence behind it.

We also touch on VO2 max, balance, flexibility and the role of consistency. A practical, evidence-based conversation for anyone serious about staying strong and independent as they age.

🌐Links in this video

Dr Schoenfeld's page https://www.lehman.edu/academics/health-human-services-nursing/exercise-sciences-recreation/bradley-schoenfeld/

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Dr. Howard Sesso of Harvard explains the results of the COSMOS trial, identifying who actually benefits from a daily multivitamin and how it impacts biological aging.

Is a daily multivitamin a life-extending "insurance policy" or just a waste of money? In this clip, Dr. Howard Sesso, Co-Principal Investigator of the landmark COSMOS trial, breaks down the clinical evidence from over 21,000 participants. We explore the "sweet spot" of nutritional insufficiency; where you aren't clinically deficient but lack the levels needed for optimal healthspan.

Dr. Sesso and Dr. Sidong Li discuss how multivitamins specifically slowed the "epigenetic clock" in individuals with existing risk factors like hypertension and accelerated biological aging. We also cover the importance of "precision nutrition" and why the synergy of essential vitamins and minerals may be more effective than high-dose single supplements. If you’re looking for a common-sense, evidence-based approach to basic supplementation, this deep dive into the Harvard-led COSMOS data provides the answers you need.

🌐Links in this video

COSMOS Trial home page https://cosmostrial.org/ Effects of daily multivitamin–multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial https://www.nature.com/articles/s41591-026-04239-3

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Senescent cells — cells that have stopped dividing but refuse to die — accumulate with age and are increasingly recognised as a key driver of age-related disease. Most people in the longevity space are familiar with senolytics like dasatinib and quercetin, but a potentially more precise approach is emerging: harnessing the immune system itself to find and eliminate senescent cells.

Dr. Amit Sharma leads the senescence immunology group at the Lifespan Research Institute, where his lab studies how natural killer cells and gamma delta T cells interact with senescent cells — and how that relationship breaks down with age. In this conversation, we explore the biology of immune surveillance of senescence, why it fails as we get older, and what his lab is doing to restore and enhance it. We also discuss the iron-ferroptosis connection, next-generation senolytics, and what the next decade might bring for senotherapy.

🌐Links in this video

Lifespan Research Institute: https://lifespanresearchinstitute.io

Dr Sharma's lab page https://lifespan.io/our-research/sharma-lab/

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Longevity researcher Nir Barzilai on what centenarians reveal about aging and the four drugs scientists believe may target it directly.

Dr Nir Barzilai has spent decades studying people who live to 100 and beyond. What he's found challenges many assumptions about aging, disease, and what we can actually do about them. In this conversation we cover what centenarian research really shows, including why they get the same diseases as the rest of us, just decades later, and what that means for the goal of longevity medicine. We then move into the practical territory: what criteria distinguish a drug that treats one disease from one that may target aging itself, which four currently approved drugs score highest on that framework, and how leading longevity physicians are beginning to use them in practice. We also discuss GLP-1 agonists in depth; their mechanisms, the emerging evidence for benefits well beyond weight loss, and the important caveats around muscle loss. Essential viewing for anyone following the science of healthy aging.

🌐Links in this video

Dr Barzilai at Albert Einstein College of Medicine https://einsteinmed.edu/faculty/484/nir-barzilai Healthy Longevity Medicine Society https://hlms.co/ American Federation for Aging Research https://www.afar.org/ Academy for Health & Lifespan Research https://www.ahlresearch.org/

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GLP-1 drugs likesemaglutide and ozempic have become household names but how much do we reallyunderstand about what they're doing inside the body? In this episode I sit downwith Dr. Mikhail Kolonin, Professor and Director of the Center for Metabolicand Degenerative Diseases at UTHealth Houston's McGovern Medical School, whoselab has spent years uncovering the deeper biology of these drugs.

We go far beyondweight loss. Dr. Kolonin explains how GLP-1 drugs trigger IL-6 signaling in fattissue, activating a thermogenic program that converts metabolically inactivewhite fat into energy-burning brown fat and how in some patients this isaccompanied by upregulation of telomerase, a protein with profound implicationsfor mitochondrial health and aging. We also tackle the muscle loss questiondirectly, examining what the latest research reveals about why lean mass losson GLP-1s exceeds simple caloric restriction, and what can realistically bedone about it.

🌐Linksin this video Dr Kolonin's page https://gsbs.uth.edu/directory/profile?id=b816c8de-c9b0-40f0-873c-42fa69db82e9

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Dr. Anurag Singh, Chief Scientific Officer at Timeline Nutrition joins Modern Healthspan for an in-depth conversation about urolithin A and the science of mitophagy, the cellular process that cleans out damaged mitochondria.

We explore the clinical evidence from multiple human trials: the ATLAS trial showing 12% muscle strength gains and 10% VO2 max improvements in sedentary middle-aged adults, independent studies in elite athletes demonstrating enhanced recovery and performance, and the groundbreaking MitoImmune trial published in Nature Aging revealing 20% increases in immune cell mitochondria in just 28 days.

Dr. Singh provides practical guidance on dosing (500mg vs 1000mg), timing, and who benefits most from supplementation. We discuss why only 30% of people can produce urolithin A naturally from foods like pomegranates and berries, and how direct supplementation overcomes this limitation.

Looking ahead, we cover Timeline's Healthspan XPrize semi-finalist status, ongoing blood-brain barrier research setting the stage for brain health trials, and Dr. Singh's vision for combining mitophagy activation with emerging therapies like mitochondrial transplantation. He also shares why he believes mitochondrial dysfunction is "the mother of all hallmarks of aging."

Whether you're interested in the science of healthy aging, considering urolithin A supplementation, or want to understand the future of longevity medicine, this comprehensive conversation provides the evidence and insights you need.

Topics covered:

• What urolithin A is and how mitophagy works

• ATLAS trial results: muscle, endurance, and inflammation

• MitoImmune trial: immune system rejuvenation

• Practical supplementation guide

• Brain health research and future directions

• The role of mitochondrial health in aging

🌐Links in this video

Time-Line home page https://www.timeline.com/ ATLAS Trial: Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults https://pubmed.ncbi.nlm.nih.gov/35584623/ Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial https://www.nature.com/articles/s43587-025-00996-x

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Dr. Valter Longo explains how fasting-mimicking diets make cancer cells vulnerable to treatment while protecting healthy tissue, plus the clinical evidence, safety protocols, and why oncologists remain skeptical.

Dr. Valter Longo, author of "Fasting Cancer," breaks down decades of research on using fasting-mimicking diets (FMD) alongside conventional cancer therapies. Cancer cannot be starved but it can be metabolically weakened by limiting resources which a the same time protects healthy cells. A process known as differential stress resistance. We cover: the mechanism behind why this works, clinical trial results in triple-negative breast cancer and other aggressive cancers, the surprising data on weight loss and cachexia, BMI cutoffs and safety protocols, how to approach your oncologist, prevention versus treatment applications, and the cutting-edge "escape pathway" research that could transform personalized cancer treatment. Dr Longo addresses the elephant in the room: why, despite promising results in both mouse models and human trials, this approach faces massive institutional and regulatory barriers to becoming standard of care. Practical, evidence-based information for patients, caregivers, and anyone interested in the intersection of nutrition and cancer biology.

🌐Links in this video

Create Cures Foundation https://createcures.org/ - Dr Longo organization in the US The Valter Longo Foundation https://www.fondazionevalterlongo.org/en/ - Dr Longo's organization in Italy and rest of the world Dr Longo's website https://valterlongo.com/ Facebook https://www.facebook.com/profvalterlongo/ Instagram https://www.instagram.com/prof_valterlongo/ Fasting Mimicking Diet company Prolon https://prolonlife.com/

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Dr. Luigi Ferrucci reveals what 60 years of Baltimore Longitudinal Study data shows about aging, inflammation, mitochondria, and the biomarkers that predict your health trajectory.In this conversation, Dr. Luigi Ferrucci, Scientific Director of the National Institute on Aging and director of the Baltimore Longitudinal Study of Aging, shares insights from the longest-running scientific study of human aging.We discuss why measuring the pace of aging matters more than a single snapshot, how mitochondrial function drives the entire aging process, and why chronic inflammation may be a secondary response rather than a primary cause of aging. Dr. Ferrucci reveals which biomarkers should be in clinical use right now (including GDF-15), what the BLSA data shows about people who age successfully, and the specific lifestyle factors that add nine years of healthy life expectancy.This is essential viewing for anyone interested in longevity science, biological age testing, and evidence-based interventions to slow aging. Dr. Ferrucci brings decades of rigorous research to questions about what actually works and what we're still learning.🌐Links in this video Dr Ferrucci's page at the NIA https://irp.nih.gov/pi/luigi-ferrucciBaltimore Longitudinal Study of Aging main site https://www.nia.nih.gov/research/labs/blsaThe Baltimore Longitudinal Study of Aging (BLSA): A 50-Year-Long Journey and Plans for the Futurehttps://pmc.ncbi.nlm.nih.gov/articles/PMC5004590/#longevity #healthspan #aging

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Dr. DanPardi explains why creatine supplementation may help preserve cognitivefunction during sleep deprivation, aging, and high mental demand, plus thespecific dosing strategies most people miss.

In thisconversation, Dr. Dan Pardi breaks down the emerging science of creatine forbrain health. While creatine is famous for athletic performance, new researchshows it may help maintain cognitive function under stress, particularly duringsleep deprivation, travel, and aging. Dr. Pardi explains the mechanisms: howcreatine acts as an energy buffer in the brain, why it works best under fatigueor high demand, and which cognitive functions respond most consistently(working memory, processing speed, sustained attention). We cover practicaldosing strategies, including why 5 grams daily may not be enough for brainbenefits, the role of loading phases, and the specific high-dose protocolstudied for sleep deprivation. This isn't about cognitive enhancement; it'sabout preservation. If you're interested in maintaining brain performance asyou age, dealing with poor sleep, or supporting cognitive resilience, thisconversation offers actionable strategies backed by research.

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Qualia LifeSciences web page https://www.qualialife.com/

Human OSwebsite https://humanos.me

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