Dr. Raghav Sehgal: Can We Measure How Fast You Are Aging?

ReProgram Episode 19: *Can We Measure How Fast You Are Aging?* 🧠 *Episode Overview* What if your age on paper is not the number that matters most? In this episode of The ReProgram, Dr. George Murphy sits down with Dr. Raghav Sehgal at the Gordon Research Conference Systems Aging Meeting in Maine. Dr. Sehgal is research faculty at Yale School of Medicine, a Forbes 30 Under 30 honoree, and one of the emerging leaders in biological age clocks, aging biomarkers, and clinical translation. The conversation begins with a simple but powerful distinction: chronological age is the number of candles on your birthday cake, while biological age asks how fast your body is changing, how risk is accumulating, and whether aging can be measured well enough to intervene. Dr. Sehgal discusses his work analyzing dozens of putative longevity interventions across epigenetic clocks, why DNA methylation data are uniquely useful for cross-study harmonization, and why some interventions may move aging biomarkers only in specific biological contexts. The episode also explores anti-retroviral therapies, inflammation-targeting drugs, rapamycin, organ-specific aging clocks, AI-driven biomarker discovery, and the future of using biological age tests in clinical care. The central message: aging clocks are not magic answers, but they may become powerful instruments for separating longevity science from longevity marketing. 🔑 *Keywords* Raghav Sehgal, biological age, chronological age, aging clocks, epigenetic clocks, biomarkers of aging, longevity interventions, geroscience, AI and aging, artificial intelligence, rapamycin, metformin, semaglutide, anti-retroviral therapy, retrotransposons, chronic inflammation, anti-TNF therapy, IL-11, lifestyle interventions, exercise, diet, supplements, follistatin gene therapy, clinical translation, precision longevity, ReProgram Podcast, Dr. George Murphy 🧠 *Takeaways* • Chronological age tells us how long we have been alive; biological age attempts to measure how fast health risk and physiological decline are progressing. • If aging cannot be quantified, it becomes difficult to test whether an intervention is actually modifying aging biology. • Epigenetic clocks are especially useful for large cross-study analyses because DNA methylation platforms are relatively standardized compared with many other omics technologies. • Dr. Sehgal describes a major harmonization effort across clinical trials and observational studies to ask which interventions move aging biomarkers. • Some surprising signals came from anti-retroviral therapy and inflammation-targeting drugs, raising questions about retrotransposons, immune activation, and chronic inflammation in aging. • Context matters: an intervention may shift aging biomarkers in one group, disease state, tissue, or organ system but not another. • Rapamycin remains promising in model organisms, but the human biomarker evidence is still more complicated and less definitive than the hype suggests.. • AI may accelerate longevity science by cleaning messy datasets, mapping aging trajectories, and helping explain why a biological age score moved. • The future of longevity medicine will depend on better biomarkers, longitudinal data, careful interpretation, and avoiding one-size-fits-all claims. 🎙️ The ReProgram Perspective This episode is a reminder that longevity science is entering a measurement era. The key question is no longer only whether an intervention sounds plausible, works in mice, or has a compelling mechanism. The harder question is whether it measurably changes human aging biology in the right person, tissue, and context. That does not mean aging clocks are perfect. They are not destiny, and they should not be treated as consumer-grade fortune telling. But used carefully, they may help us ask better questions: Which intervention affects which pathway? Which organ system is changing? Which signal reflects disease correction, lifestyle mismatch, or a deeper aging mechanism? The promise of the field is not just to tell someone they are “younger” or “older” than expected. The promise is to understand why that signal is changing and what, if anything, can be done about it. *Chapters* 02:33 Introduction from the Systems Aging GRC 03:02 Biological Age vs Chronological Age 04:28 Testing 51 Longevity Interventions 06:20 Why Epigenetic Clocks? 08:12 Anti-Retroviral Therapy, Retrotransposons, and Aging 10:36 The Role of Inflammation in Aging 12:23 What Counts as a True Longevity Signature? 15:08 Rapamycin, Humans, and the Evidence Gap 16:31 Surprising Findings From the Study 18:19 Aging Clocks in the Clinic 19:47 AI, Big Data, and Longevity Science 22:32 Raghav’s Personal Health Transformation *Notes* Dr. Sehgal's Website: https://www.raghav-sehgal.com/ Dr. Sehgal's 51 Interventions Paper: https://www.biorxiv.org/content/10.1101/2024.10.22.619522v1.full TranslAGE: https://www.translage.io/