“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,” Raghav Sehgal said, Science Daily reported. Scientists at Yale University have identified which interventions genuinely influence biological aging and which show little measurable benefit, according to a study published in Nature Medicine.
The research team analyzed findings from 51 clinical studies involving over 110 DNA methylation biomarkers and 16 major epigenetic clocks. By examining measurements taken before and after various treatments, the investigators determined that certain prescription medications and lifestyle modifications reduce biological age. Popular over-the-counter supplements examined in the analysis, however, showed little evidence of producing similar effects.
The project began when Sehgal shifted his research focus from cancer to the aging process at the Yale School of Medicine. Working in the laboratory of assistant professor Albert Higgins-Chen, the team set out to evaluate existing anti-aging strategies. “For the first time we’ve shown that certain therapies have measurable impacts,” Sehgal said, Science Daily reported.
Yale Researchers Use Epigenetic Clocks to Measure Biological Age
To measure biological age, the Yale team relied primarily on blood-based measurements called epigenetic clocks. These tools analyze chemical patterns attached to DNA, specifically methyl groups that act like tags. Previous research shows these chemical markers change as people grow older. Computer algorithms use those changes to estimate a person’s functional age, which may differ from chronological age.
The study reviewed four main categories of interventions: prescription drugs, lifestyle modifications, over-the-counter supplements, and medical procedures. The strongest reductions in biological age markers were associated with specific pharmaceutical treatments. These included metformin and semaglutide, along with anti-TNF therapies that target an immune-system protein involved in inflammation.
“What we did was pretty unique,” Sehgal said, Science Daily reported. The researchers combined data from retrospective analyses, animal models, and real-world clinical studies to identify which interventions slow down aging across known biomarkers.
Diet and Exercise Reduce Epigenetic Age More Effectively
Diet and exercise emerged as another clear area of success in reducing epigenetic age. Combining regular physical activity with a healthy eating plan consistently produced favorable changes in aging biomarkers. The dietary approaches examined by the team included Mediterranean, low-fat, and low-carb eating plans.
In contrast, the analyzed over-the-counter supplements and certain medical procedures failed to produce measurable reductions in biological age. The researchers also discovered that newer biological age clocks performed better than older versions. Participants living with diseases generally experienced larger changes in their aging biomarkers than healthy participants.
The next priority for the research team is testing these findings in larger, more diverse populations. This step will help investigators determine how consistently different treatments influence biological age across people with varying health conditions and backgrounds. Validated blood tests could drastically 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,” Sehgal said, Science Daily reported. Instead of waiting decades for clinical trial results, researchers might identify effective interventions in a few years or months.
Senior author Higgins-Chen emphasized the need for caution when interpreting these biomarker shifts. “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,” Higgins-Chen said, Science Daily reported.
Unanswered Questions in Aging Research
Despite these promising findings, major questions remain regarding the exact mechanisms driving these changes. Researchers must still establish whether alterations in biological age are directly caused by a treatment or influenced by uncounted factors. Additional studies must determine how quickly changes occur and whether they persist after treatment ends.
“And most importantly – what does the change mean for our long-term risk of age-related disease and functional decline?” Higgins-Chen said, Science Daily reported.
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