A growing body of scientific research increasingly suggests that aging may be far more flexible than once believed. Challenging the traditional view that getting older is a rigid, unalterable trajectory, scientists at Yale University have now taken an important step forward in identifying which specific interventions can actually influence biological aging and which ones show little to no measurable benefit.
According to their new findings, certain prescription medications and targeted lifestyle changes are capable of reducing biological age as measured by sophisticated DNA-based blood tests. However, popular over-the-counter supplements examined in the comprehensive research showed little evidence of producing the same protective or reversing effects.
The findings, which were recently published in the scientific journal Nature Medicine, could significantly help researchers evaluate potential anti-aging treatments more effectively. Even so, the study authors emphasize an essential caveat: changes in biological age markers do not yet automatically mean that people will live longer lives or successfully avoid age-related diseases. The research marks a critical milestone in understanding how to measure human aging, but establishing a direct link to lifespan extension remains a hurdle for future scientific exploration.
From Fighting Cancer to Understanding Aging
When Raghav Sehgal began his graduate studies at Yale several years ago, his initial professional trajectory pointed toward oncology. He planned to leverage advanced computer science techniques to investigate cancer, drawing upon a solid academic background in engineering and practical experience launching a computational biology startup. That foundation gave him the robust analytical tools needed for complex biomedical data.
However, a single, probing question from his Ph.D. adviser at the Yale School of Medicine fundamentally shifted his research direction. Instead of focusing exclusively on individual, isolated diseases such as cancer or cardiovascular disease, why not investigate the underlying aging process itself—the very engine that contributes to the development of these chronic conditions in the first place?
"That put me on a different path," said Sehgal, who now serves as an associate research scientist in psychiatry with a specialization 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 studies the complex biological mechanisms driving human aging, how scientists can reliably measure those microscopic changes, and why getting older drastically increases the likelihood of debilitating conditions like cancer, diabetes, and dementia. His work also explores whether medical and lifestyle interventions might successfully reverse certain aspects of biological age, even if completely halting or eliminating the natural aging process itself remains far beyond human reach.
New DNA Tests Reveal Which Anti-Aging Treatments Work
Sehgal serves as the lead author of the new study, which was conducted within the laboratory of Albert Higgins-Chen, an assistant professor of psychiatry at the Yale School of Medicine. The research team set out to resolve a longstanding debate in longevity science: determining which existing approaches to slowing aging actually produce physiological changes that can be reliably and objectively measured.
Their extensive analysis found encouraging results for certain targeted medications and structured lifestyle interventions. In contrast, the over-the-counter dietary supplements included in the broad study generally failed to produce any meaningful reductions in biological age.
The collaborative project involved members of the entire Higgins-Chen laboratory, including researchers Daniel Borrus, Jenel F. Armstrong, John Gonzalez, Jessica Kasamoto, and Yaroslav Markov, who combined their expertise to analyze vast pools of disparate clinical data.
"For the first time we’ve shown that certain therapies have measurable impacts," Sehgal noted. "This wasn’t previously possible, because we didn’t have enough data to say these biomarkers are consistently responsive to these interventions."
Biomarkers act as vital biological indicators, providing measurable information about what is happening dynamically inside the human body. In the specialized field of aging research, these indicators help scientists estimate an individual’s biological or functional age, a metric that can frequently diverge significantly from their chronological age based on birth certificates.
How Scientists Measure Biological Age
To rigorously investigate whether various treatments could influence the aging trajectory, the Yale team relied primarily on advanced blood-based measurements commonly known as epigenetic clocks.
These sophisticated tools analyze chemical patterns attached directly to human DNA, focusing particularly on methyl groups—basic chemical structures that function like molecular tags. Previous scientific research has demonstrated that these chemical patterns shift in predictable ways as people grow older. Certain lifestyle or medical interventions may possess the capacity to reverse specific age-associated patterns, and specialized computer algorithms use those detected changes to estimate a person’s current biological age.
To build their study, the researchers synthesized findings from 51 distinct clinical trials investigating a wide array of anti-aging strategies. These diverse approaches ranged from dietary supplements and prescription medications to sweeping lifestyle changes and specialized medical procedures.
Across those comprehensive studies, the team examined more than 110 DNA methylation biomarkers, which included 16 major epigenetic clocks. By directly comparing biological measurements taken before and after interventions, the researchers could accurately evaluate which clinical approaches were reliably associated with measurable reductions in biological age.
"What we did was pretty unique," Sehgal explained. "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?
To make sense of the vast data, the researchers categorized the evaluated interventions into four main groups: prescription drugs, lifestyle modifications, over-the-counter supplements, and specialized medical procedures.
One of the clearest and most consistent findings involved diet and physical exercise. Combining regular physical activity with a healthy, balanced eating plan consistently reduced epigenetic age across the board. The specific dietary approaches examined in the data included well-established regimens such as the Mediterranean diet, low-fat diets, and low-carb diets.
However, the strongest and most pronounced reductions in biological age markers were strongly associated with certain pharmaceutical treatments. These included metformin and semaglutide—prescription medications primarily used to manage metabolic conditions, blood sugar levels, and body weight—as well as anti-TNF therapies, which specifically target a key protein involved in the human body’s inflammatory response.
Tumor necrosis factor, commonly referred to as TNF, is an essential immune-system protein that normally helps the body fight inflammation-related injury, but chronic overactivation can accelerate tissue damage.
Conversely, the findings proved far less encouraging for over-the-counter supplements and certain medical procedures. Within the analyzed clinical studies, these popular consumer approaches generally failed to produce any measurable reductions in epigenetic age.
Furthermore, the researchers uncovered subtle technical nuances, finding that newer generations of biological age clocks performed more accurately than older versions. Another critical discovery was that participants living with diagnosed diseases generally experienced larger, more pronounced shifts in their aging biomarkers compared to healthy study participants.
Could DNA Blood Tests Transform Anti-Aging Research?
According to Sehgal, the immediate priority for the research team is to rigorously test these findings in larger, more diverse human populations. Doing so will help scientists determine how consistently different treatments influence biological aging across demographic groups with varying underlying health conditions and ethnic backgrounds.
The development of these improved blood tests could also dramatically shorten the timeline required to evaluate potential anti-aging therapies in a clinical setting.
"If these new biomarkers are eventually validated to predict long-term health, scientists will be able to evaluate anti-aging therapies much faster," Sehgal 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 represents a profound paradigm shift for aging research. Instead of relying entirely on traditional clinical studies that must follow human participants for decades to observe mortality or disease incidence, scientists might eventually utilize validated biological age measurements to identify promising treatments much earlier in the pipeline.
However, senior author Albert Higgins-Chen stressed that the scientific community must remain cautious when interpreting what shifts in aging biomarkers actually mean in practical terms.
"肴e 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," Higgins-Chen said. "However, the true meaning of that change must be fully understood."
Important Questions About Slowing Aging Remain
Although the results generated by the Yale team are undeniably promising, several major scientific questions remain unanswered.
For instance, researchers still need to establish definitive proof regarding whether changes in biological age are directly and mechanistically caused by a treatment, or if they are influenced by confounding variables that were not fully accounted for in the original clinical trials. Scientists also need to better understand how quickly those physiological changes occur, whether the effects persist long after a treatment is stopped, and which precise biological mechanisms drive them.
Most importantly, researchers have not yet established whether successfully lowering epigenetic age directly leads to meaningful, long-term improvements in overall health, functional independence, or resistance to age-related illnesses.
"And most importantly—what does the change mean for our long-term risk of age-related disease and functional decline?" Higgins-Chen reiterated.
Further scientific investigations aimed at answering these pressing questions are currently underway, with additional studies being led by Yale researchers Daniel Borrus, Jenel F. Armstrong, and Grace Zou.
The Higgins-Chen laboratory maintains formal affiliations with Yale’s Department of Pathology, the Computational Biology and Bioinformatics Program, and the Y-Age Yale Center for Research on Aging, positioning the institution at the forefront of modern longevity science.
What Appears to Work Against Biological Aging?
Based on the improved DNA-based blood tests and the comprehensive meta-analysis, the Yale researchers identified several standout approaches for reducing biological age markers. Structured lifestyle changes—specifically regular physical activity paired with healthy dietary frameworks like the Mediterranean, low-fat, or low-carb diets—showed consistent positive impacts.
Additionally, powerful prescription medications, including metabolic drugs like metformin and semaglutide alongside anti-TNF therapies, demonstrated the strongest reductions in epigenetic age. Meanwhile, the widely used over-the-counter supplements and certain medical procedures tested in the research showed little to no measurable effect on halting or reversing cellular aging.
These results provide a much clearer, data-driven picture of which interventions may genuinely influence biological aging. Nevertheless, researchers caution that extensive further investigation is vital to confirm these findings and determine whether reductions in biological age markers ultimately translate into fewer age-related diseases, sustained vitality, or extended human lifespans.