A growing body of research suggests that aging may be more flexible than once believed. Now, scientists at Yale have taken an important step toward identifying which treatments can actually influence biological aging and which ones show little measurable benefit.
Their findings suggest that certain prescription medications and lifestyle changes can reduce biological age as measured by DNA-based blood tests. Popular over-the-counter supplements examined in the research, however, showed little evidence of producing the same effects.
The findings, published in Nature Medicine, could help scientists evaluate anti-aging treatments more effectively, although researchers emphasize that changes in biological age markers do not necessarily mean people will live longer or avoid age-related diseases.
From Fighting Cancer to Understanding Aging
When Raghav Sehgal began graduate school at Yale several years ago, he planned to use advanced computer science techniques to investigate cancer. His background in engineering and experience launching a computational biology startup had given him a strong foundation for that work.
However, a question from his Ph.D. adviser at the Yale School of Medicine changed his research direction. Rather than focusing on individual diseases such as cancer or cardiovascular disease, why not investigate the aging process that contributes to their development?
“That put me on a different path,” said Sehgal, now an associate research scientist in psychiatry who specializes 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.”
Sehgal now studies the biological mechanisms behind human aging, how scientists can measure those changes, and why getting older increases the likelihood of conditions such as cancer, diabetes, and dementia. His work also explores whether interventions might reverse certain aspects of biological aging, even if eliminating aging itself remains beyond reach.
New DNA Tests Reveal Which Anti-Aging Treatments Work
Sehgal is the lead author of the new study, which was conducted in the laboratory of Albert Higgins-Chen, an assistant professor of psychiatry at the Yale School of Medicine. The research team set out to determine which existing approaches to slowing aging produce changes that can be reliably measured.
Their analysis found encouraging results for certain medications and lifestyle interventions. In contrast, the over-the-counter supplements included in the study generally failed to produce meaningful reductions in biological age.
The project involved the entire Higgins-Chen laboratory, including Daniel Borrus, Jenel F. Armstrong, John Gonzalez, Jessica Kasamoto, and Yaroslav Markov.
“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 provide measurable information about what is happening inside the body. In aging research, they can help estimate a person’s biological or functional age, which may differ from their chronological age.
How Scientists Measure Biological Age
To investigate whether treatments could influence aging, the Yale team relied primarily on blood-based measurements called epigenetic clocks.
These tools analyze chemical patterns attached to DNA, particularly methyl groups (basic chemical structures that act like tags). Previous research has shown that these chemical markers change as people grow older. Some interventions may reverse certain age-associated patterns, and computer algorithms use those changes to estimate a person’s biological age.
The researchers brought together findings from 51 clinical studies investigating different anti-aging strategies. These ranged from dietary supplements and medications to lifestyle changes and medical procedures.
Across those studies, the team examined more than 110 DNA methylation biomarkers (including 16 major epigenetic clocks). By comparing measurements taken before and after interventions, they could evaluate which approaches were associated with reductions in biological age.
“What we did was pretty unique,” Sehgal said. “We already know that certain things might prolong health span and lifespan. There is data from retrospective analysis as well as from 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.”
Which Anti-Aging Treatments Showed the Best Results?
The researchers divided the interventions into four main groups: prescription drugs, lifestyle modifications, over-the-counter supplements, and medical procedures.
One of the clearest findings involved diet and exercise. Combining regular physical activity with a healthy eating plan consistently reduced epigenetic age. The dietary approaches examined included Mediterranean, low-fat, and low-carb diets.
The strongest reductions in biological age markers were associated with certain pharmaceutical treatments. These included metformin and semaglutide, prescription medications used to manage metabolic conditions and body weight, as well as anti-TNF therapies that target a protein involved in the body’s inflammatory response.
(TNF, or tumor necrosis factor, is an immune-system protein that helps fight inflammation-related injury.)
The findings were less encouraging for over-the-counter supplements and some medical procedures. In the studies examined, these approaches did not produce measurable reductions in epigenetic age.
The researchers also discovered that newer biological age clocks performed better than older versions. Another important finding was that people living with diseases generally experienced larger changes in their aging biomarkers than healthy participants.
Could DNA Blood Tests Transform Anti-Aging Research?
According to Sehgal, the next priority is to test these findings in larger, more diverse populations. This would help researchers determine how consistently different treatments influence biological aging across people with different health conditions and backgrounds.
The improved blood tests could also dramatically shorten the time needed to evaluate potential anti-aging therapies.
“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.”
That possibility could represent a major advance for aging research. Instead of relying entirely on clinical studies that follow participants for decades, scientists might eventually use validated biological age measurements to identify promising treatments much earlier.
However, senior author Higgins-Chen stressed that scientists must be careful about interpreting what changes in aging biomarkers actually mean.
“We have developed a rigorous, systematic approach to evaluating and comparing how biomarkers change across a wide variety of interventions, and that is a critical step in the right direction,” he said. “However, the true meaning of that change must be fully understood.”
Important Questions About Slowing Aging Remain
Although the results are promising, several major questions remain unanswered.
For example, researchers still need to establish whether changes in biological age are directly caused by a treatment or influenced by other factors that were not accounted for. They also need to understand how quickly those changes occur, whether they persist after treatment ends, and which biological processes produce them.
Most importantly, scientists have not yet established whether lowering epigenetic age leads to meaningful improvements in long-term health.
“And most importantly – what does the change mean for our long-term risk of age-related disease and functional decline?” Higgins-Chen said.
Further investigations into these questions are underway, with additional studies led by Borrus, Armstrong, and Grace Zou.
The Higgins-Chen laboratory is also affiliated with Yale’s Department of Pathology, the Computational Biology and Bioinformatics Program, and the Y-Age Yale Center for Research on Aging.
What Appears to Work Against Biological Aging?
Based on the improved DNA-based blood tests, the Yale researchers identified two particularly promising approaches for reducing biological age markers:
- Prescription medications: Drugs used for metabolic regulation and weight management, including metformin and semaglutide, were among the treatments associated with the strongest reductions in biological age.
- Healthy eating combined with exercise: Regular physical activity paired with nutritious diets, including Mediterranean, low-fat, and low-carb eating plans, consistently produced favorable changes in aging biomarkers.
The analysis also identified benefits from certain anti-TNF medications, while the tested over-the-counter supplements and some medical procedures showed little measurable effect.
These results provide a clearer picture of which interventions may influence biological aging. However, more research is needed to confirm the findings and determine whether reductions in biological age markers ultimately translate into fewer age-related diseases, better health, or longer lives.
