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

Summary

In this podcast episode, the host and guest discuss the factors that contribute to centenarians living to be 100 years old or more. They explore the role of genetics and the environment in determining lifespan, and the differences between people who live to be 70 or 80 versus those who live to be 90 or 100. The guest, who has studied centenarians extensively, explains that genes play a significant role in living to be 100, and that there are certain disease-sparing variants that seem to protect centenarians from age-related diseases. The discussion also touches on the relationship between low birth weight and reduced lifespan, and the impact of lifestyle factors such as smoking and exercise on longevity.

The speakers also discuss the idea of using genetics to understand aging and lifespan. They mention a thought experiment involving 10,000 people with perfect genes randomized into three groups: one living a normal life, one doing everything bad for their health, and one doing everything right. They also discuss the concept of centenarians and their health span, which is the period of time they live without age-related diseases. The speakers point out that while centenarians may die quickly once they become sick, they have a compression of morbidity, meaning they are sick for a shorter period of time than non-centenarians.

The discussion covers various topics related to endocrinology, genetics, and longevity. The conversation explores the possibility of a protective factor in individuals with a lower RPM and a slower metabolism. The importance of looking at the genetics of resiliency and the association of certain genes with longevity and diseases such as Alzheimer's is also discussed. The importance of a polygenic approach to risk assessment for diseases is highlighted, and the need for more research on longevity genes is emphasized. The conversation also touches on the possibility of recruiting 10,000 centenarians and their offspring for research purposes.

The speakers also discuss the use of metformin for anti-aging purposes. They explain that they are conducting a study called TAME to establish a target that is similar to aging, and metformin is being used for this purpose. However, the speakers also note that metformin can have potential limitations on cardiorespiratory fitness and strength gains, especially for individuals who exercise regularly. The speaker suggests that metformin may be more beneficial for older individuals or those who are biologically older. The study also looks at the impact of metformin on muscle growth and transcriptome changes, with trade-offs between less muscle growth but healthier muscle. The speakers acknowledge that the TAME study may not fully answer the question of metformin's benefits for healthy individuals, as the study population is primarily older and less healthy.