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

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Apr 25, 2022

Nir Barzilai, M.D., the Director of the Institute for Aging Research at Albert Einstein College of Medicine, shares groundbreaking insights about longevity. He reveals genetic clues from centenarians, discussing how specific gene variants contribute to long lifespans. The conversation explores the TAME trial, emphasizing the potential of metformin as a longevity tool and its varied impacts on health. Barzilai also touches on epigenetic clocks and the controversial role of NAD precursors in aging, inviting listeners to reconsider their understanding of what it means to live a longer, healthier life.

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INSIGHT

Genetics of Longevity

Genes significantly influence lifespan, especially when comparing lifespans over 90 to those over 100, relative to 70 or 80.
Genes don't appear to have a major impact between 70 and 80 years old.

INSIGHT

Longevity Genes

Centenarians possess protective genes, or "longevity genes," that contribute to their extended lifespans.
These genes not only promote longevity but also offer protection against disease-causing genes.

INSIGHT

GH and IGF-1 Signaling

Growth hormone (GH) and IGF-1 signaling pathway impairment is common in centenarians.
About 60% of centenarians have genetic variations impacting this pathway.

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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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