Beyond Longevity

A bowhead whale can live for more than 200 years. How does its body hold up for that long? Daphna Stern speaks with Dr Mirre Simons, an evolutionary biologist at the University of Sheffield who studies why some animals age faster than others.Dr Simons co-authored a study in Nature that points to one possible answer: bowhead whale cells are unusually good at repairing damaged DNA. Our own cells make a version of one of the proteins that helps the whale do this.The conversation explores why large animals get far less cancer than their size alone would predict, a puzzle known as Peto’s paradox. Daphna and Dr Simons also discuss when a cell’s response to stress might help or harm, and what animal studies of intermittent fasting and rapamycin can tell us about human ageing. They look at whether telomeres or a single test score can tell us how fast we are ageing, and discuss new research that found a shift towards longer lipid chains with age in humans and other species.About the guestDr Mirre J. P. SimonsSchool of Biosciences, University of Sheffield, UKDr Simons is an evolutionary biologist and senior lecturer at the University of Sheffield. He earned his PhD at the University of Groningen in the Netherlands. His lab uses fruit flies and compares findings across species to understand why animals age differently and what those differences might teach us about human ageing. His research on diet and ageing has been supported by a Sir Henry Dale Fellowship from Wellcome and the Royal Society. He co-authored the bowhead whale DNA repair study in Nature and the study on lipid chain length and ageing in Nature Aging.Links* Dr Mirre Simons at the University of Sheffield* Simons Lab* Dr Mirre Simons on LinkedInPapersDNA repair in the long-lived bowhead whale | Nature (2025)Why the body loses its ability to regulate itself with age | Ageing Research Reviews (2026)The integrated stress response and lifespan in fruit flies | PNAS (2026)Dietary restriction and longevity across fruit fly species | EMBO Reports (2026)Does reproduction come at the cost of survival? Evidence from birds | eLife (2025)Rapamycin and survival after infection in mice | GeroScience (2023)Lipid chain length and ageing across species | Nature Aging (2026)Chapters00:00 Welcome and the Bowhead Whale01:44 Why Study Ageing in Animals?03:42 How Does Evolution Explain Ageing?06:54 How Do Bowhead Whales Repair Damaged DNA?10:02 The Human and Whale Versions of CIRBP13:02 Peto’s Paradox and Cancer Risk in Large Animals17:26 Can DNA Repair Backfire?21:18 The Integrated Stress Response26:54 Intermittent Fasting: Meal Timing or Eating Less?30:35 Refeeding After Dietary Restriction31:50 Dietary Variety vs Consistency32:49 Rapamycin and mTOR Basics34:33 Rapamycin and Survival After Infection in Animals36:08 What Would Human Rapamycin Trials Need to Show?37:17 Can Telomeres Tell Us How Fast We Are Ageing?40:58 What Do Telomeres Actually Do?43:13 Can One Number Capture Biological Age?45:27 How Lipid Chain Length Changes With Age47:43 Do Longer Lipid Chains Contribute to Ageing?51:12 Next Steps for Lipid Research Across Species54:26 The Future of Longevity Research57:14 Rapid-Fire Questions58:56 Closing Reflections

Billions are flowing into longevity and biotech, but how do investors tell a genuine breakthrough from an expensive scientific dead end? Sergey Jakimov, founding and managing partner of LongeVC, joins Daphna Stern on Beyond Longevity to explain how investors decide which companies deserve backing. He says his team has reviewed almost 5,000 companies since 2021 and invested in only a tiny fraction.Sergey shares the problems he sees again and again: overstated science, weak intellectual property and no credible route through clinical trials and regulatory approval. He also explains why some early longevity investors lost money, what AI can realistically change in drug discovery, and why clinical trial results do not always reflect patients’ quality of life. Throughout, he argues that longevity companies must ultimately prove themselves by treating real diseases.About the guestSergey Jakimov is a founding and managing partner of LongeVC, an investment firm focused on early-stage biotech and longevity, backing companies developing medicines for conditions including cancer, heart disease and diseases of the brain.He has co-founded three deep-tech companies, including the health-data company Longenesis, and co-founded the Longevity Science Foundation. His LongeVC biography credits him with raising more than $50 million for his own ventures and through his work as an entrepreneur in residence. Longenesis reports that its tools have supported more than half a million participants in the UAE's Emirati Genome Programme.LinksLongeVC: https://longevc.com/linkedin.com/in/jakimovChapters00:00 How Do Investors Judge Longevity Science?01:50 Sergey’s Experience of Neurological Illness04:12 Treating Disease or Targeting Ageing?06:33 From Engineering to Biotech09:06 Why Clinical Trials Struggle to Recruit Patients13:35 How Biotech Investors Choose What to Back17:00 Why Results in Mice Can Fail in Humans20:17 Alzheimer’s Drugs and the Amyloid Debate23:01 Biotech Due Diligence Red Flags28:17 Family Offices and the Risks of Longevity Investing30:13 Investing Through a Specialist Biotech Fund31:27 Why Specialisation Matters in Biotech32:12 Why LongeVC Backs So Few Companies33:13 Biotech Fund Timelines and Exits34:13 Computing Power, Manufacturing and Clinical Trial Bottlenecks36:42 What Can AI Really Change in Drug Discovery?38:47 Why LongeVC Invested in Rubedo39:30 How Do Longevity Treatments Get Regulatory Approval?44:26 How Much Money Does a Biotech Company Need?47:30 How Investors Decide on Follow-on Funding49:27 How Venture Capital Investors Support Founders51:43 European and US Venture Capital Compared54:11 Rapid Fire on Joy, Exercise and Longevity Myths57:02 From Promising Science to Useful Treatments

Why do joints fail as we age, and why, after decades of research, is there still no drug that reliably stops osteoarthritis from progressing?Daphna Stern speaks with Maria Kyriazi, a DPhil researcher at the University of Oxford studying ageing and osteoarthritis.Still in her twenties, Maria gives us a view of science that we do not often hear. She talks openly about experiments that fail after months of work, almost having to give up her Oxford DPhil because she could not fund it, and the pressures young scientists face to produce and publish exciting results.They also discuss why osteoarthritis is far more complicated than the old idea of “wear and tear”, what ageing changes inside our joints, why promising research has repeatedly failed to become effective treatments, and whether we might eventually be able to treat the disease itself rather than simply manage the pain.About the guestMaria Kyriazi is a DPhil student in Molecular and Cellular Medicine at the University of Oxford, where she researches the age-related mechanisms involved in osteoarthritis. Originally from Athens, she came to the UK to study Biomedical Genetics at Newcastle University before completing an MRes in Ageing and Health and moving into doctoral research at Oxford.In October 2026, Maria received the Korenchevsky Prize for her research into ageing and osteoarthritis at the British Society for Research on Ageing annual scientific meeting. She previously won the Young Star Award at the Greek International Women Awards. She is a Mellon Longevity Graduate Scholar at Oriel College and an Onassis Foundation Scholar.Her research examines how ageing processes, including autophagy and cellular senescence, change within the joint and may contribute to the development of osteoarthritis.Maria Kyriazi — Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal SciencesAlsaleh Group | Ageing in the musculoskeletal system and beyond earth — Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences00:00 Why study ageing and osteoarthritis?01:38 How did Maria get from Athens to Oxford?06:32 Why study ageing itself?09:59 What actually happens in osteoarthritis?14:00 Is osteoarthritis caused by ageing or injury?17:06 What happens when cellular recycling starts to fail?19:40 Why have osteoarthritis treatments repeatedly failed?22:12 What does scientific failure really look like?30:32 Why is it so difficult to fund a scientific career?39:30 Does funding pressure encourage scientists to oversell results?41:57 How do young scientists protect research integrity?44:52 Could we eventually treat osteoarthritis itself?49:02 Rapid-fire questions51:43 Closing reflections

Exercise in a Pill? How Muscle Could Protect Memory, with Professor Constanza J CortesEpisode SummaryCould your body get some of the benefits of a workout without you doing the exercise? And could a drug like that help prevent memory loss or treat Alzheimer’s?Host Daphna Stern speaks with Professor Constanza J Cortes, a neuroscientist at the University of Southern California, about how exercise could help preserve memory as we age. Professor Cortes’ goal is to develop treatments for people who cannot exercise enough because of pain, illness or limited mobility.Her research starts with muscle. During exercise, muscles release chemical messengers that travel around the body, including to the brain. Professor Cortes is testing whether a drug, sometimes described as an exercise mimetic, could reproduce some of those signals without the need to exercise. Her team has already improved memory and other brain outcomes in mouse models of Alzheimer’s by changing what happens in their muscles.But her latest research also raises an important question: does a brain affected by Alzheimer’s still respond to exercise in the same way as a healthy brain? In mouse studies, exercise triggered some of the expected molecular changes but did not lead to the same improvements in memory or broader protection of the brain.We discuss how much of exercise a drug could realistically reproduce, whether healthy people could benefit, what still needs testing in humans, differences between how male and female muscle responds to exercise, and her ambition to have a treatment in the clinic within 10 years.About the GuestProfessor Constanza J Cortes is an Assistant Professor of Gerontology at the University of Southern California and leads the Cortes Lab at the USC Leonard Davis School of Gerontology. Her research focuses on exercise, brain ageing, Alzheimer’s disease and the signals that pass between skeletal muscle and the brain.She is principal investigator of a National Institute on Aging-funded research programme investigating exercise-associated signalling against brain ageing and Alzheimer’s disease. Her work also examines sex differences in how the body responds to exercise. In 2026, she received the Women in AGE Scientific Achievement Award in recognition of her contributions to ageing research.Research Mentioned in This EpisodeSkeletal muscle TFEB signalling promotes central nervous system function and reduces neuroinflammation during ageing and neurodegenerative diseaseCell Reports, 2023Research showing how activating TFEB in skeletal muscle can reproduce some effects associated with exercise and influence the ageing brain.https://pubmed.ncbi.nlm.nih.gov/37952157/Activation of the muscle-to-brain axis ameliorates neurocognitive deficits in an Alzheimer’s disease mouse model via enhancing neurotrophic and synaptic signalling2024Research identifying prosaposin (PSAP) as part of the muscle-to-brain signalling pathway and examining PS18 as a potential way to reproduce some of its effects.https://pubmed.ncbi.nlm.nih.gov/39269584/Long-term voluntary exercise reveals limited translation of hippocampal molecular responses into neuroprotection in 5xFAD micebioRxiv preprint, 2026Research examining why an Alzheimer’s disease brain may respond differently to prolonged exercise, despite showing some molecular signs of an exercise response.https://pubmed.ncbi.nlm.nih.gov/42817989/Single-nuclei RNA-sequencing uncovers sexually divergent exercise signatures partially mimicked by TFEB overexpression in mouse skeletal musclebioRxiv preprint, 2026Research showing substantial differences between male and female skeletal muscle responses to exercise and TFEB activation.https://pubmed.ncbi.nlm.nih.gov/41659513/Further ReadingNational Geographic: Why exercise can help keep the brain healthyhttps://www.nationalgeographic.com/magazine/article/new-clues-are-revealing-why-exercise-can-keep-the-brain-healthyUSC Leonard Davis School of Gerontology: Professor Cortes on understanding the effects of exercise on the brainhttps://gero.usc.edu/2023/04/13/assistant-professor-constanza-cortes-understanding-the-effects-of-exercise-on-the-brainUSC: Constanza Cortes receives the 2026 Women in AGE Scientific Achievement Awardhttps://gero.usc.edu/2026/10/01/constanza-cortes-phd-receives-women-in-age-scientific-achievement-awardThe Cortes Lab at USChttps://gero.usc.edu/labs/corteslabTimestamps* 00:00 Introduction and episode overview* 01:37 Welcome and Professor Cortes’s background* 02:30 Why the ageing brain became her focus* 03:58 Does exercise work differently in the ageing brain?* 05:39 How does muscle communicate with the brain?* 07:22 What do muscles tell the brain when you run?* 09:35 Can muscle signals released during exercise improve memory?* 11:28 Could PS18 mimic exercise’s effects on the brain?* 12:25 The ongoing study in ageing mice* 14:25 What is PSAP, and what does it normally do in the body?* 16:03 Does the PSAP in blood really come from muscle?* 17:56 What changes inside muscle when we exercise?* 20:22 Which benefit of exercise would she most want to turn into a treatment?* 22:04 Could an exercise mimetic prevent Alzheimer’s or treat it?* 23:19 Could a healthy person benefit?* 25:05 Can changing muscle protect the brain in Alzheimer’s?* 27:21 Why running did not rescue memory in Alzheimer’s mice* 29:07 Can the diseased brain still hear the signal?* 30:01 Do fewer Alzheimer’s plaques necessarily mean better memory?* 31:29 What can people with Alzheimer’s do today?* 32:36 What needs proving before human studies* 33:47 How much does AI help her research?* 37:32 What the first human study needs to show* 39:19 When the biomarkers improve but the person does not feel better* 43:10 When could an exercise pill reach the market?* 44:22 What “exercise in a pill” really means* 46:23 Concerns about off-label use* 48:08 The unanswered question: sex differences in exercise* 50:20 Where will the research be in 10 years?* 51:58 Rapid-fire questions* 53:16 Closing thoughts

Everyone talks about living longer. Far fewer people ask what happens if we reach those extra decades without purpose, identity, relevance or a clear idea of what we actually want to do with them.In this episode of Beyond Longevity, I speak with Paul Long, a third-generation storyteller, former major-market television reporter, anchor and special projects producer, and Emmy-winning content creator. He went on to run his own production company before making a major pivot in his own life.Paul now runs New Way Forward, a platform helping people rethink the second half of life, not just financially, but around purpose, health, relevance, contribution and continued income. His starting point is simple: the traditional path of work, retirement and gradual withdrawal no longer makes much sense if people may have decades of active life ahead of them.We discuss why retirement can leave people struggling once the initial honeymoon period wears off, why losing identity and relevance may matter as much as losing income, and why financial planning alone does not prepare people for what comes next. We also look at who tends to reach this point, whether reinvention is realistic when someone is already in survival mode, and what society needs to change as people live longer.Paul shares practical tools he uses himself, including an adapted Wheel of Life exercise and writing a letter from your 95-year-old self. And rather than advocating one dramatic leap, he explains why small, repeated actions may be a much more realistic way to build a different life.About the guestPaul Long began his career in television news, working as a major-market reporter, anchor and special projects producer. He later became an Emmy-winning content creator, receiving an Emmy for Best Documentary for A Passing of the Torch, and founded his own production company, producing work for major companies.Around 2006, Paul began seriously questioning what he wanted the next stage of his own life to look like. That process eventually led to New Way Forward, where he now shares the ideas, tools and lessons he has gathered on purpose, health, income and reinvention in the second half of life. New Way Forward is still in launch mode, with content across YouTube, LinkedIn, Substack and its own website.Site: www.NewWayFWD.comYouTube: https://www.youtube.com/@newwayfwd/videosLinkedIn: https://www.linkedin.com/in/paul-long-nwf/Substack: https://newwayfwd.substack.com/Chapters00:00 Who Is Paul Long?01:42 What Is New Way Forward?03:11 Why Does Awareness Come Before Answers?07:15 Who Starts Looking for a New Direction?11:42 What Can the Wheel of Life Tell You?15:02 How Do You Find the Common Thread in Your Life?17:47 What Forces Us to Reinvent Our Lives?22:11 The Different Versions of Paul Long24:09 Why Can Retirement Leave People Unhappy?29:08 Why Does Relevance Matter as We Age?30:29 Why Does Pleasure Fade So Quickly?30:40 What Creates Lasting Satisfaction?32:23 Who Is New Way Forward Designed For?36:39 Which Tools Help People Reinvent Their Lives?38:48 Can Small Steps Really Change Your Life?40:56 What If You Are Just Trying to Survive?44:29 Can Society Adapt to Longer Lives?47:52 How Do Identity, Meaning and Regret Change With Age?52:33 How Can People Use New Way Forward?54:44 How Do You Move Past Fear and Start?57:10 Rapid-Fire Longevity Questions01:01:09 What Makes a Good Second Half of Life?