Why do some people remain sharp and mobile into their 90s while others struggle with diabetes, memory loss, or mobility problems decades earlier? A new study led by the University of Colorado Boulder may have part of the answer. Researchers have identified more than 400 genes linked to frailty, a broad term that describes the physiological decline that comes with aging. Their work, published in Nature Genetics, could open the door to more personalized treatments that tackle aging at its roots.
What the Researchers Found
Until now, scientists had only identified 37 genes tied to unhealthy aging. This latest study expands that number to 408. Using a genome-wide association study, the team analyzed DNA and health records from hundreds of thousands of participants in the UK Biobank and other datasets. They found that different sets of genes drive different forms of frailty, from poor cognition and metabolic issues to disability and even limited social support.
“This is the largest study yet to use genetics to try to do that,” explained Isabelle Foote, the first author and a postdoctoral researcher at CU’s Institute for Behavioral Genetics. Foote, who once worked as a nurse in elder care, said she often saw patients the same age respond in dramatically different ways to illness and injury. “Why was this happening to them and not the person next to them who was the same age and got to go home? We really didn’t have a lot of answers.”
Redefining Frailty
More than 40 percent of adults over 65 in the U.S. are considered frail. Doctors typically score frailty on a 30-point scale that measures everything from walking speed to grip strength. But this approach is imperfect. Two people can have the same frailty score yet face completely different challenges. One may be physically weak but mentally sharp, while another may be mobile but cognitively impaired.
“Aging is not just one thing. There are many ways to be frail,” said Dr. Kenneth Rockwood, a frailty expert at Dalhousie University in Canada and a co-author of the study. By distinguishing subtypes of frailty, doctors may be able to tailor care more effectively and researchers can better understand the biology of decline.
The team identified six categories of frailty: disability, poor cognition, metabolic problems, multiple diseases, generally unhealthy lifestyle, and limited social support. For example, the SP1 gene, associated with immune function and Alzheimer’s disease, was strongly linked to poor cognition. Meanwhile, the FTO gene, long known for its ties to obesity, appeared to underlie several different aging subtypes.
The Promise of Personalized Treatments
Senior author Andrew Grotzinger, assistant professor of psychology and neuroscience at CU Boulder, believes this research could change how we approach aging-related disease. “What this paper does is not only identify sub-facets of disordered aging but also demonstrate that there is very different biology underlying them,” he said. “The tangible next step is to figure out how to treat this underlying biology.”
Foote envisions a future where individuals receive a “polygenic risk score” that predicts what type of aging problems they are most likely to face. Someone flagged as cognitively frail, for example, could begin therapies to prevent dementia years earlier. A person prone to metabolic frailty could take steps to prevent diabetes or heart disease.
Is an Anti-Aging Pill Possible?
The idea of a single pill to slow or reverse aging may still be a fantasy, but targeted treatments are becoming more realistic. Rather than one magic cure, there may eventually be specialized therapies addressing different aspects of aging.
“This paper suggests that it’s probably not going to be a single magic pill to address all the diseases that come with aging,” said Grotzinger. “But maybe it doesn’t need to be hundreds anymore.”
For now, the findings reinforce the “geroscience hypothesis” — that the key to fighting multiple chronic illnesses is to treat aging itself. As scientists uncover the molecular pathways behind frailty, they may finally be able to slow the clock that governs the decline of the human body.
