When Jeanne Calment passed away at 122, her habits; smoking, wine, and a generally active lifestyle; didn’t neatly fit existing longevity theories. Her remarkable lifespan suggests genetic as well as lifestyle factors can tip the scales toward healthy aging. But systematically studying human longevity is difficult: large-scale, long-term studies are expensive and time-consuming.
Scientists have turned to animal models, but a new study in Aging Cell takes a different approach—using cells from human “super-agers.” Researchers tapped the New England Centenarian Study, the largest database of centenarians and their families, collecting blood cells from 45 people who reached the far extremes of both age and health.
They reprogrammed these cells into induced pluripotent stem cells (iPSCs), preserving each donor’s genetic code. The result is a unique biobank for uncovering genetic signatures associated with a long, healthy life.
Before reprogramming, researchers tested participants with aging clocks that measure a person’s biological age (how well their bodies function). Centenarians averaged a biological age six and a half years below their chronological age. However, even within families, some children inherited a “longevity signature,” while others did not. Despite concerns that reprogramming very old cells might fail, the new iPSCs were healthy, retained most of their genetic integrity, and could generate various cell types. A few male centenarians’ cells did show partial loss of the Y chromosome, a known phenomenon in older males that may elevate disease risk.
Because iPSC reprogramming erases cells’ epigenetic marks; the chemical tweaks that turn genes on or off; scientists can study the underlying genetic code of exceptionally long-lived individuals. Transforming the centenarian-derived iPSCs into cortical neurons, for instance, showed these cells better resisted toxic protein buildup linked to age-related cognitive decline and diseases like Alzheimer’s. Other experiments are exploring how centenarian-derived astrocytes; a type of supportive brain cell increasingly implicated in dementia; might protect against neurodegeneration.
Crucially, these iPSC lines are linked to individual donors’ medical, cognitive, and lifestyle histories. This lets researchers choose cells best suited for studying diverse aspects of aging across tissues—brain, muscle, heart, and immune system. The resulting data may shed light on why centenarians maintain better health in extreme old age, potentially leading to therapies that replicate their protective genetic traits or bolster resilience against age-related diseases.
Ultimately, this centenarian stem cell biobank stands to expand our grasp of human longevity. By offering a window into the genetics behind ultra-healthy aging, it paves the way for new interventions that could slow or modify the aging process—helping more people attain the elusive goal of living not just longer, but healthier lives.