The concept of extremely long life, popularised in films like Highlander, may seem like pure fiction, however; researchers are actively studying centenarians (people who have lived to 100) to uncover the biological and environmental factors that contribute to their exceptional longevity.

Centenarians present a unique opportunity for researchers to explore longevity, as they demonstrate an impressive resilience to illness and injury, according to George Murphy, a stem-cell biologist at the Boston University Chobanian & Avedisian School of Medicine. Murphy recounts the remarkable case of a centenarian who not only survived the 1912 Spanish flu but also recovered from Covid-19 twice. One prevailing theory suggests that centenarians may possess a genetic composition that shields them from various diseases.

Centenarian stem cell research

A research team at the University of Boston (BU), announced in November 2024 that they had developed a groundbreaking resource for studying aging by reprogramming stem cells from the blood of centenarians. Induced pluripotent stem cells (iPSCs) are cells that have been reprogrammed to have the ability to develop into different types of cells in the body. They hold great potential for regenerative medicine and studying diseases.

These iPSCs allow scientists to investigate how centenarians maintain resilience against aging-related diseases. Early findings suggest that neurons derived from centenarians’ iPSCs exhibit robust stress-response mechanisms, potentially explaining their ability to avoid diseases like Alzheimer’s.             

As people age, their cells may not be as effective at controlling the production of proteins, which can increase the risk of developing diseases. Recent findings, which are yet to be published, indicate that brain cells taken from individuals over 100 years old were less active in regulating protein production compared to cells from younger individuals. However, when these centenarian-derived cells were exposed to a stressful situation, they were able to activate their quality control mechanisms quickly and effectively, sorting out harmful proteins from beneficial ones at a faster rate.

3D brain models of Alzheimer’s disease

In 2014, Harvard Medical School scientists Doo Yeon Kim and Rudolph Tanzi developed 3D brain models of Alzheimer’s disease using brain cells from centenarians and compared them to models made from cells from people in their 60s.

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In initial investigations, it was discovered by researchers that brain cells from centenarians exhibit elevated levels of genes linked to defence against Alzheimer’s disease, as stated by Doo Yeon Kim.

The New England Centenarian Study (NECS)

The NECS, led by Dr. Thomas T. Perls at BU, has been studying centenarians since 1995. The study’s findings suggest that genetics play a significant role in reaching 100 years, with centenarians often possessing variants that protect against age-related diseases. Centenarians like Millie Flashman, a participant in the NECS study, exemplify the protective genetic factors and lifestyle habits that contribute to longevity.

The NECS has also established a comprehensive longevity database to examine familial trends and uncover patterns that promote resilience to aging across generations. While genetics play a key role in exceptional longevity, environmental and behavioural factors are also crucial.

Dr Perls has developed the acronym “SAGEING” to highlight actionable factors like proper sleep, exercise, nutrition, and stress management that can improve life expectancy for the general population. The aim of studying centenarians is to use their findings to develop treatments and strategies that can improve the quality of life for older individuals. By uncovering the ways in which centenarians’ cells are protected, we may be able to learn how to age healthily ourselves.