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As a nurse working in an elder care facility, Isabelle Foote saw it every day: Some people age better than others.

Some eased into their 90s with mind and body intact, while others battled diabetes, Alzheimer’s or mobility issues decades earlier. Some could withstand a bad fall or bout of the flu with ease, while others never left the hospital again.

“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,” said Foote, who left that job to become a geneticist.

In a paper published this month , Foote, now a postdoctoral associate at �山����’s Institute for Behavioral Genetics, provides some clues.

Isabelle Foote left her job as an elder care nurse to use genetics to better understand aging.

She and an international team of co-authors have identified more than 400 genes associated with accelerated aging across seven different sub-types. The study reveals that different groups of genes underlie different kinds of disordered aging, a.k.a. frailty, ranging from cognitive decline to mobility issues to social isolation.

The findings lend support to what is known as the “geroscience hypothesis” — the idea that to treat the multiple chronic illnesses that come with aging, we must treat aging itself.

“To be able to identify treatments to stop or reverse accelerated biological aging, you need to know what the underlying biology is,” said Foote, first author on the paper. “This is the largest study yet to use genetics to try to do that.”

Redefining 'frailty'

The study centers around “frailty,” a catch-all term for the “multisystem physiological decline” that often comes with aging.

More than 40% of U.S. adults over age 65 are considered frail.

Doctors typically assess frailty using a 30- point index that measures everything from walking speed and grip strength to number of diagnosed illnesses and amount of social activity. The problem with this approach, said Foote, is that two people can get the same high frailty score even though one is cognitively sharp but can’t walk and another is in good physical health but has a poor memory.

This lack of distinction has made it hard for doctors to make recommendations for aging adults and for scientists to pinpoint the underlying causes of unhealthy aging.

“Aging is not just one thing. There are many ways to be frail,” said Dr. Kenneth Rockwood, a leading expert in frailty, based at Dalhousie University in Nova Scotia, Canada and co-author on the study. “The question then becomes: What genes are involved?”

To find out, the team conducted a “genome-wide association study” analyzing DNA and health information from hundreds of thousands of participants in the and other public datasets to see which genes were associated with 30 frailty symptoms.

They identified 408 genes associated with accelerated aging/frailty, a significant increase from the 37 genes previously identified.

Some genes, they found, were strongly linked to certain subtypes of unhealthy aging, including: “disability”; “poor cognition”; “metabolic problems” (like diabetes and heart disease); “multiple diseases”; “generally unhealthy lifestyle”; and “limited social support”.

For instance, the SP1 gene, associated with immune function and Alzheimer’s disease was strongly associated with the broad “poor cognition” subtype, whereas the FTO gene, a gene known to be associated with obesity, seemed to underly several different subtypes.

“What this paper does is not only identify sub-facets of disordered aging but also demonstrate that there is very different biology underlying them,” said senior author Andrew Grotzinger, assistant professor of psychology and neuroscience at �山����. “The tangible next step is to figure out how to treat this underlying biology.”

An anti-aging pill?

In the near term, the authors suggest that clinical measurements of frailty—which often shows up long before specific diseases—be expanded to include the six subtypes.

That way, someone diagnosed as cognitively frail could be guided toward therapies to prevent dementia, while someone frail in the metabolic domain might take steps to prevent diabetes or heart disease.

Foote envisions a day when people could get a “polygenic risk score” offering more detailed insight into what kind of unhealthy aging they are prone to.

But the holy grail, she says, would be to identify the molecular pathways that drive aging itself and develop therapies to put the brakes on.

Is a single anti-aging pill on the horizon?

Not likely, the authors say.

But could there one day be a pill to treat a package of age-related metabolic issues, and another to address numerous cognitive issues?

It’s a tantalizing idea, said Grotzinger, and genetic research could pave the way.

“This paper suggests that it’s probably not going to be a single magic pill to address all the diseases that come with aging, but maybe it doesn’t need to be hundreds anymore.”