Episode #386: Longevity Myths- Biological Clocks, GLP-1 Muscle Loss, and What Actually Predicts Lifespan
Episode Description
The longevity industry is now worth over $100 billion per year. From DNA methylation clocks to multi-cancer blood tests and GLP-1 medications, the promises are bold.
But what actually predicts lifespan?
In this episode, Dr. Jordan Feigenbaum and Dr. Austin Baraki break down the science behind biological clocks, the real story on GLP-1–related muscle loss, and introduce the Barbell Medicine “Vital Five” — a clinically grounded framework for health and longevity.
Key Points:- The Three Generations of Biological Clocks: Understanding the evolution of DNA methylation tests from simple chronological markers (Horvath) to sophisticated predictors of mortality (GrimAge) and functional decline (DunedinPACE).
- Descriptive vs. Prescriptive Metrics: Why a biological age score acts as a lagging indicator rather than a tool for clinical decision-making, compared to traditional risk factors like blood pressure and ApoB.
- GLP-1s and Sarcopenia Reality: A nuanced look at lean mass loss during semaglutide and tirzepatide treatment, emphasizing the difference between total lean mass and actual skeletal muscle quality.
- Weight-Independent Benefits of Incretins: Analyzing data from the SELECT and FLOW trials regarding the direct cardioprotective and renal benefits of GLP-1 receptor agonists.
- The Limitations of Early Detection: Why multi-cancer early detection (MCED) tests can lead to diagnostic loops and how clinical utility differs from marketing promises.
- The Barbell Medicine Vital Five: A definitive framework for longevity focusing on blood pressure, ApoB, VO2 max, relative strength, and body composition.
- Neurodegenerative Research Outlook: A critical review of the EVOKE trials and the potential (or lack thereof) for current weight-loss medications in treating established Alzheimer's disease.
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- 00:00 Overview: longevity industry and proxy metrics
- 01:06 Biological age and DNA methylation clocks
- 08:18 Clinical usefulness and limitations of biological age testing
- 16:16 Multi-cancer early detection tests: screening tradeoffs
- 30:39 Exercise prescription for longevity (treat-to-target)
- 54:39 Protein intake and longevity: evidence and recommendations
- 1:07:23 GLP-1 receptor agonists: outcomes, misconceptions, and use cases
- 1:34:24 Hormone therapy (women and men): risks, benefits, evidence
- 1:49:19 Practical longevity tracking: “Vital Five” markers
- 1:58:15 Closing
- Biological Clock
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8853656/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC12038942/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11424583/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6366976/
- Cancer Screening
- https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.5574
- https://www.thelancet.com/article/S1470-2045(23)00277-2/fulltext
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01700-2/fulltext
- https://www.nhs-galleri.org/
- Exercise
- https://bjsm.bmj.com/content/56/13/755
- https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2807854
- https://pubmed.ncbi.nlm.nih.gov/35442242/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8915309/?mc_cid=87bfcaaa3a&mc_eid=8786146256
- https://pmc.ncbi.nlm.nih.gov/articles/PMC9012529/
- https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428
- https://pubmed.ncbi.nlm.nih.gov/35228201/
- https://pubmed.ncbi.nlm.nih.gov/35662329/
- https://academic.oup.com/biomedgerontology/article/77/4/781/6354429
- https://www.sciencedirect.com/science/article/abs/pii/S0025619625001004
- https://pmc.ncbi.nlm.nih.gov/articles/PMC12131147/
- https://pubmed.ncbi.nlm.nih.gov/18595904/
- https://pubmed.ncbi.nlm.nih.gov/12242311/
- Protein
- https://pubmed.ncbi.nlm.nih.gov/40418846/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7250948/
- https://pubmed.ncbi.nlm.nih.gov/39110456/
- https://pubmed.ncbi.nlm.nih.gov/24606898/
- https://www.bmj.com/content/370/bmj.m2412
- GLP-1
- https://www.cell.com/cell-metabolism/abstract/S1550-4131(26)00008-2
- https://www.nejm.org/doi/full/10.1056/NEJMoa2307563
- https://www.nejm.org/doi/abs/10.1056/NEJMoa2403347
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)01296-0/fulltext
- https://link.springer.com/article/10.1007/s11154-025-09991-4
- https://pmc.ncbi.nlm.nih.gov/articles/PMC12338914/
- HRT
- https://pubmed.ncbi.nlm.nih.gov/25754617/
- https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00211-6/abstract
- https://www.nejm.org/doi/full/10.1056/NEJMoa2215025
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4527564/
- https://www.mdpi.com/1422-0067/25/22/12221
- Body Roundness Index (BRI) : https://www.barbellmedicine.com/blog/should-bri-replace-bmi/
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