Study reveals which interventions might help
By Karen Guzman, Yale University
Edited by Sadie Harley,
reviewed by Robert
Egan
When Raghav Sehgal arrived at Yale as a graduate student several years ago, he wanted to explore the use of powerful computer science tools in cancer research. With an engineering background and a computational biology startup already under his belt, he was well prepared.
But as Sehgal began his Ph.D. studies, his thesis adviser at
the Yale School of Medicine posed a larger question: If you want to solve
cancer or any age-related disease, such as cardiovascular disease, why not
solve aging itself?
"That put me on a different path," said Sehgal, an
associate research scientist in psychiatry with specialties in computational
biology and bioinformatics. "As researchers, we have a long way to go in
understanding the aging process and whether the steps we take to manage it
really work."
Today, Sehgal's research focuses on the biological systems
that drive human aging and how to best measure aging, as well as why aging
gives rise to diseases like cancer, diabetes and dementia. And while his
research might not necessarily solve aging, he does explore whether the aging
process can be reversed through interventions.
Testing which interventions truly register
In a new paper, Sehgal's research team took a significant
step toward determining which existing anti-aging measures have quantifiable
impacts. Using a new class of DNA-based blood tests, they found that lifestyle
interventions and certain drug treatments appear to slow the aging process,
while over-the-counter supplements don't have much effect.
"For the first time we've shown that certain therapies
have measurable impacts," said Sehgal. "This wasn't previously
possible because we didn't have enough data to say these biomarkers are
consistently responsive to these interventions." Biomarkers are measurable
indicators that reflect a person's functional or biological age rather than
just the number of years lived.
For their analysis, the researchers primarily used a type of
blood-based biomarker known as epigenetic
clocks, which estimate epigenetic or biological age by measuring the
pattern of methyl groups (basic chemical structures that act like tags)
attached to a person's DNA.
As people age, these chemical tags change, previous research
has shown. Successful anti-aging interventions can reverse the tags. Computer
algorithms are then able to use the changes observed in these tags to estimate
a person's epigenetic "age."
Drugs and lifestyle stood out
In their work, the researchers combined data from 51
anti-aging intervention studies—which examined a range of strategies, from
supplements to medical procedures—and measured more than 110 DNA methyl
biomarkers (including 16 major epigenetic clocks). They then compared
participants' biological ages before and after various interventions.
"What we did was pretty unique," Sehgal said.
"We already know that certain things might prolong health span and
lifespan. There are data from retrospective analyses as well as animal models.
We took all that knowledge along with the real-world clinical studies to
identify which interventions in humans were slowing down aging across the board
in these known biomarkers."
The researchers tested four categories of intervention:
pharmacological drugs, lifestyle-based changes, over-the-counter supplements
and medical procedures. They found that lifestyle interventions, such as a
combination of a healthy diet (whether it's Mediterranean, low-carb or low-fat)
and exercise, consistently decreased epigenetic age.
Pharmacological interventions—including metformin and
semaglutide, prescription medications used for metabolic control and weight
management, and anti-TNF therapies, which use biologic medications to target an
immune system protein that triggers harmful inflammation—decreased epigenetic
age the most. (TNF, or tumor necrosis factor, is an immune system protein that
helps fight inflammation-related injury.)
On the other hand, over-the-counter supplements and certain
medical procedures didn't decrease epigenetic age, their analysis showed. Other
key findings revealed that the newer biological age clocks outperformed older
models and that biomarkers changed more in people with diseases than in healthy
volunteers.
Faster answers may be possible
Going forward, the next step would be expanded testing to
measure interventions and their impact on a widespread, diverse group of
volunteers, Sehgal said.
"If these new biomarkers are eventually validated to predict
long-term health, scientists will be able to evaluate anti-aging therapies much
faster," he added. "Instead of waiting decades for evidence from
clinical trials, we'll be able to see which interventions are effective and in
which people in a few years or even months."
Publication details
Raghav Sehgal et al, Responsiveness of epigenetic aging
biomarkers to longevity interventions in humans, Nature Medicine (2026). DOI:
10.1038/s41591-026-04562-9
Journal information: Nature Medicine
