<p class="p2"><span class="s1"><a href="https://peterattiamd.com/nirbarzilai2/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220425-pod-nirbarzilai&utm_content=220425-pod-nirbarzilai-podfeed"> View the Show Notes Page for This Episode</a></span></p> <p class="p2"><span class="s1"><a href="https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220425-pod-nirbarzilai&utm_content=220425-pod-nirbarzilai-podfeed"> Become a Member to Receive Exclusive Content</a></span></p> <p class="p2"><span class="s1"><a href="https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=220425-pod-nirbarzilai&utm_content=220425-pod-nirbarzilai-podfeed"> Sign Up to Receive Peter's Weekly Newsletter</a></span></p> <p class="p3">Nir Barzilai, Director of the Institute for Aging Research at the Albert Einstein College of Medicine, is back for his third appearance on The Drive. In this episode, Nir divulges insights into lifespan and healthspan through the lens of his extensive research on centenarians as well as the latest from the TAME trial (Targeting/Taming Aging with Metformin), a multi-center study investigating the concept that the multi-morbidities of aging can be delayed in humans. He discusses common gene variants found in centenarians, important pathways for longevity, and ultimately what we can learn from centenarians about extending lifespan while also trying to improve healthspan. Additionally, Nir goes into depth on metformin as a longevity tool for humans, including studies with positive and negative results. He discusses the impact metformin can have on exercise for both strength training and cardiovascular training, as well as future research facilitated by data from the TAME Trial. He also touches on epigenetic clocks and concludes with his take on the usefulness of NAD precursors as a potential gero-protective agent.</p> <p class="p3">We discuss:</p> <ul class="ul1"> <li class="li3">Insights from genetic studies of centenarians and twins [3:00];</li> <li class="li3">Genes with protective variants that aid longevity [13:00];</li> <li class="li3">The relationship between growth hormone and IGF-1 [22:45];</li> <li class="li3">Use of growth hormone as a longevity tool [34:00];</li> <li class="li3">Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45];</li> <li class="li3">The correlation between high TSH and longevity [46:30];</li> <li class="li3">Important pathways for longevity [52:00];</li> <li class="li3">Insights from centenarian studies, nature vs. nurture, and more [59:00];</li> <li class="li3">The contraction of morbidity that comes with improved healthspan [1:08:00];</li> <li class="li3">Defining healthspan [1:13:13];</li> <li class="li3">Unique perspectives and positive attitudes of centenarians [1:17:30];</li> <li class="li3">Lessons to take away from centenarians [1:24:00];</li> <li class="li3">Metformin overview: history, studies, and potential for gero-protection [1:28:45];</li> <li class="li3">The TAME trial (Targeting Aging with Metformin) [1:39:00];</li> <li class="li3">The challenge of studying metformin in animals models [1:46:45];</li> <li class="li3">How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30];</li> <li class="li3">The search for biomarkers to identify who can benefit from treatment [2:00:30];</li> <li class="li3">The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30];</li> <li class="li3">Are NAD precursors geroprotective? [2:21:30]; and</li> <li class="li3">More.</li> </ul> <p class="p1">Connect With Peter on <a href="https://twitter.com/PeterAttiaMD">Twitter</a>, <a href="https://www.instagram.com/peterattiamd/">Instagram</a>, <a href="https://www.facebook.com/peterattiamd/">Facebook</a> and <a href="https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg">YouTube</a></p> <p class="p1"> </p>
Actionable Insights
1. Prioritize Ultra-Primary Prevention
Focus on preventing chronic diseases long before they manifest, as secondary prevention (after a disease onset) is not true prevention. This is considered the most important lesson from centenarians for extending healthspan and lifespan.
2. Embrace Exercise and Nutrition
For most individuals, the fundamental path to longevity involves consistent exercise and thoughtful nutrition, regardless of genetic predispositions.
To explore metformin as a potential geroprotective agent, share relevant scientific papers (e.g., Nir Barzilai’s 2016 and 2020 Cell Metabolism papers) with your doctor to initiate a discussion about its suitability for you.
To minimize potential gastrointestinal side effects, take metformin in small doses with food, ideally after the first bite when your stomach is already full.
If you are biologically young or highly active, consider that metformin might not be beneficial for you, as it could potentially blunt some of the positive adaptations from exercise.
Based on studies showing significant effects, metformin may be beneficial for individuals starting around age 50, although the TAME study is recruiting people aged 65-79.
7. Senolytics After 70-80
Avoid taking senolytics before the age of 70 or 80, as their benefits are likely targeted towards older populations.
8. Cautious TSH Treatment in Elderly
If an elderly person has an incidental finding of TSH between 5 and 8 with normal thyroid hormones, it may be a physiological adaptation, and immediate treatment is not always necessary.
9. Question Biological Age Clocks
Do not rely on biological age clocks for individual guidance or therapeutic decisions, as they are easily manipulated, not mechanistic, and lack sufficient validation for guiding interventions.
10. Caution with NAD Precursors
Exercise caution when considering NAD precursors (NR, NMN) due to a lack of clear biological understanding of their mechanism, inconsistent animal study results, and concerns about preparation stability and efficacy.
11. Explore Podcast Membership
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