SuperAgers and Centenarians: What Can They Tell Us About Longevity?

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In order to understand how we can extend our healthspans and lifespans far beyond the current norm, some researchers turn to those who have already succeeded. What makes centenarians and ”SuperAgers” – people who age more slowly than others – different from the rest of us?

Dr. Nir Barzilai is the director of the Einstein Institute for Ageing Research and leader of the TAME trial of the longevity enhancing effects of metformin. He is a pioneer in the study of centenarians and how they age at the cellular level, seeking to discover how centenarians’ genes can help us slow ageing or protect against age-related diseases. Here, he talks about his research in relation to drug discovery and COVID-19:

Dr. Nir Barzilai: SuperAgers are people who have aged more slowly than others. In other words, SuperAgers’ chronological age does not reflect their biological age. They do not accumulate age-related disease and require treatment, which allows them to work longer, enjoy post-retirement interests, to live life to the fullest.

In my studies, not only did SuperAgers live twenty to thirty more healthy years, they also had a contraction of morbidity. This means they spent less time being sick and therefore there is a ‘longevity dividend’ among SuperAgers as medical costs are saved.

Identifying genes associated with longevity can gives us clues as to the biological mechanisms involved, helping to guide the development of anti-ageing drugs:

The interesting thing about discovering specific changes in the genes of centenarians and their offspring is that those genes can point to a mechanism that can be targeted for intervention. We can look to these mechanisms for developing drugs that inhibit or stimulate these genes.

Through the Longevity Genes Project at Einstein, we have found two such changes in genes that control the good aspect of lipid metabolism. These discoveries led to the development of a drug and successful Phase 2 studies by the pharmaceutical companies Merck and Ionis. [Barzilai is on Merck’s advisory board.] The indications for the development of these drugs was cardiovascular disease, but they may impact other diseases as well.

Centenarians are quite capable of surviving COVID-19. The two hallmarks of ageing with which Covid mortality seems to be most strongly linked are immune system decline and increased inflammation. Centenarians tend to experience these hallmarks to a lesser degree than most.

Centenarians, as well as many older adults, do survive COVID-19. While we must be sensitive to the range of socioeconomic factors impacting how and who COVID-19 is affecting in America, it’s important to look at the ‘hallmarks of aging.’’

On a cellular level, these hallmarks are processes that are considered to be the core underlying machinery controlling how our bodies age. COVID-19 vulnerability is linked to two of the hallmarks of aging: immune decline and inflammation. Some older adults experience these hallmarks at lower levels.

Further, research has shown that immunity among offspring of centenarians is better than that of others their age. Because all hallmarks of aging are involved, not just the immune system, these individuals are able to survive through a severe disease like COVID-19.

According to Dr. Barzilai, the possibility of growing older without growing sicker is within our reach:

I always say that a future of healthy aging is not just a hope, but a promise: not only have we gone from the promise of targeting aging, but there are drugs that can do this in use by humans today. Those drugs can change biological age and improve immunity — not only against COVID-19, but against the next pathogen.

For example, metformin is a drug that can target aging in humans. There are several papers that show COVID-19 patients on metformin were hospitalized less and had lower mortality than patients with similar problems who were not treated with metformin. We need to move rapidly to consider available drugs like this that can help defend older adults against threats like COVID-19 now and those in the future.

This also why we need the TAME Trial. At fourteen leading research institutions across the country, we hope to engage over three thousand individuals between the ages of sixty-five and seventy-nine to test whether those taking metformin experience delayed development or progression of age-related chronic diseases such as heart disease, cancer, and dementia.

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