#204 - Centenarians, metformin, and longevity | Nir Barzilai, M.D.

The Peter Attia Drive

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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.

We discuss:

• Insights from genetic studies of centenarians and twins [3:00];
• Genes with protective variants that aid longevity [13:00];
• The relationship between growth hormone and IGF-1 [22:45];
• Use of growth hormone as a longevity tool [34:00];
• Longevity genotypes: the role of APOE e2, Lp(a), Klotho, and CETP [41:45];
• The correlation between high TSH and longevity [46:30];
• Important pathways for longevity [52:00];
• Insights from centenarian studies, nature vs. nurture, and more [59:00];
• The contraction of morbidity that comes with improved healthspan [1:08:00];
• Defining healthspan [1:13:13];
• Unique perspectives and positive attitudes of centenarians [1:17:30];
• Lessons to take away from centenarians [1:24:00];
• Metformin overview: history, studies, and potential for gero-protection [1:28:45];
• The TAME trial (Targeting Aging with Metformin) [1:39:00];
• The challenge of studying metformin in animals models [1:46:45];
• How data from the TAME trial could provide insights into biomarkers of aging and facilitate a future study on proteomics [1:53:30];
• The search for biomarkers to identify who can benefit from treatment [2:00:30];
• The impact of metformin on exercise, and finding the right indication for the use of metformin [2:10:30];
• Are NAD precursors geroprotective? [2:21:30]; and
• More.

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