Dr. Nir Barzilai—Genetics and Lifestyle Factors of Centenarians

By Longevity by Design, November 11, 2022

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Aging research is quickly evolving to understand how we can live healthier, longer lives. Scientists are looking to centenarians and their family members to reveal how their environment, lifestyle, and genetics contribute to their delayed aging.

In this episode of Longevity by Design, our co-hosts, Dr. Gil Blander and Ashley Reaver, are joined by Dr. Nir Barzilai,  Director of the Institute for Aging Research at the Albert Einstein College of Medicine. Tune in as Dr. Nir Barzilai describes how he pursued a career in aging, where the research stands on metformin and longevity, and the Longevity Genes Project, genome mapping 750 centenarians and their family members to understand the genetic component of aging.


Meet Longevity by Design’s podcast guest, Dr. Nir Barzilai

Dr. Nir Barzilai is the director of the Institute for Aging Research at the Albert Einstein College of Medicine, the Director of the Paul F. Glenn Center for the Biology of Human Aging Research, and of the National Institutes of Health’s (NIH) Nathan Shock Centers of Excellence in the Basic Biology of Aging. He is a professor in the Departments of Medicine and Genetics, and member of the Diabetes Research Center and of the Divisions of Endocrinology & Diabetes and Geriatrics.

Dr. Nir Barzilai recounted going for walks with his 68-year-old grandfather as a kid and wondered if there were ways to slow down aging so that he would be quick and agile at his grandfather's age. Today, Dr. Barzilai’s research interests are in the biology and genetics of aging. He focuses on genes of exceptional longevity, and has demonstrated that centenarians have protective genes, delaying aging and offering protection against age-related diseases.

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The Longevity Genes Project

Dr. Nir Barzilai's team researched 500 healthy elderly people between the ages of 95 and 112 and their children. This study aimed to identify longevity genes that could eventually lead to new, targeted drug therapies that significantly delay age-related diseases such as Alzheimer's, type 2 diabetes, and cardiovascular disease. In this episode of Longevity by Design, Dr. Nir Barzilai discusses some of the major takeaways from this research initiative.


Hypotheses on why centenarians have exceptionally long lives

Dr. Nir Barzilai describes two research hypotheses his team had as to how centenarians live exceptionally long and healthy lives: 

  1. Centenarians are doing everything we should do in terms of our environment. They exercise and eat the right things. They have the "Blue Zone" kind of lifestyle, and maybe that's why they live to be 100.
  2. Centenarians may have the “perfect genome.” For example, they may not have the genetic risk of genetic SNPs commonly associated with age-related diseases like Alzheimer's, cardiovascular disease, and cancer.

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Research findings from 750 centenarians and their families

Dr. Nir Barzilai found that centenarians and their families had unusually high levels of a cardioprotective blood biomarker. “One of the things that came up almost immediately, in the first ten centenarians and then, again, in the next 20 centenarians is that these families have very high HDL cholesterol.”

“The average HDL cholesterol levels are 45 in men and 55 in women. These people had HDL cholesterol levels above 100, up to 150, so this is a really important marker. So, we started to look for genotypes associated with HDL cholesterol, and we found two genotypes that were very interesting.”

Interestingly, growth hormones may also play a role in aging. "We used data from the UK Biobank on the important growth hormone—IGF-1. And we showed that when you're young, it protects you against various diseases and mortality. And when you're old, it's the opposite."

This research showed that IGF-1 levels in centenarians were potentially predictive of aging. "Women who had the lowest growth hormone levels when they were old lived twice as long as the women with the highest growth hormone level."


Metformin targets the hallmarks of aging

Metformin is a drug best known for improving blood sugar levels in people with type II diabetes. Metformin has caught the attention of aging researchers as a potential pharmaceutical agent that can delay aging. 

“Human studies show that Metformin can extend lifespan and healthspan, and it's shown to have a significant effect on diabetes, cancer, and cardiovascular disease prevention, and even the prevention of cognitive decline and mortality.”

 Dr. Nir Barzilai acknowledges how this must sound, "You think that one drug can do all of this? You're crazy! Now, let me explain how one drug has so many actions targeting these diseases. Metformin targets all of the hallmarks of aging. When you fix one hallmark of aging, others are affected as well. For example, Metformin targets the mitochondria, shifts metabolic outcomes, and can even prevent some oxidative damage and reduce inflammation." 

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Advice on living a healthier longer life

As a scientist who has spent a significant amount of time with centenarians, Dr. Nir Barzilai's tips on living a healthier, longer life are particularly insightful. Dr. Barzilai recounts that personality and outlook on life are particularly striking. He describes one 100-year-old, "He is thoughtful, talks about his life, thinks his son is great, and thinks his daughter-in-law cannot do wrong. He's really wonderful."

He goes on to show that mindset is everything, "Old people are very interested in being happy, and it doesn't take a lot to make them happy. In young people, you need five things to make them happy for every bad thing. In the elderly, you only need one or two things to make them happy."

Dr. Nir Barzilai also mentions that intermittent fasting for at least 16 hours per day is beneficial for aging. In addition, he’s noticed personal benefits from intermittent fasting, such as improved some of the phenotypic factors related to aging, like exercise capacity.



Longevity by Design

Longevity by Design is a podcast for individuals looking to experience longer, healthier lives. In each episode, Dr. Gil Blander and Ashley Reaver join an industry expert to explore a personalized health journey. The show helps you access science-backed information, unpack complicated concepts, learn what’s on the cutting edge of longevity research and the scientists behind them. Tune into Longevity by Design and see how to add years to your life, and life to your years.


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