Faculty and principal Investigator, Raghav Sehgal originally came to Yale hoping to apply computer science to cancer. With an engineering background and experience building a computational biology startup, Sehgal was well positioned to investigate the disease through data. His research direction changed when his thesis adviser at the Yale School of Medicine posed a more ambitious question — If aging contributes to cancer, cardiovascular disease, diabetes, and dementia, could targeting aging itself help address several diseases at once? “That put me on a different path,” said Sehgal, an associate research scientist in psychiatry who specialises 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 investigates the biological systems that drive human aging, how scientists can measure the process, and whether interventions can reverse some of its effects. He is the first author of a new study from the laboratory of Albert Higgins-Chen, an assistant professor of psychiatry at the Yale School of Medicine.
The team examined whether widely studied anti-aging strategies produce consistent changes in biological age. Unlike chronological age, which simply counts years, biological age attempts to capture how quickly the body’s cells, tissues, and organs are changing. Using DNA-based blood tests, the researchers found measurable improvements after lifestyle programs and several prescription treatments. The over-the-counter supplements included in the analysis, however, generally showed little effect.
The findings were published in Nature Medicine. “For the first time we’ve shown that certain therapies have measurable impacts. This wasn’t previously possible, because we didn’t have enough data to say these biomarkers are consistently responsive to these interventions,” Sehgal said. The analysis centered on epigenetic clocks, blood-based tools that estimate biological age by examining DNA methylation. Methyl groups (basic chemical structures that act like tags) attach to DNA and help regulate how genes behave without changing the underlying genetic code. These patterns shift predictably with age.
Algorithms can analyse them to produce estimates of epigenetic age, while more specialized biomarkers may reflect inflammation, immune function, or other aspects of physical decline. A younger reading does not necessarily mean someone will live longer, but it can show whether an intervention is affecting biological processes associated with aging. The researchers pooled data from 51 intervention studies, covering approaches that ranged from dietary supplements to medical procedures. They assessed more than 110 DNA methylation biomarkers (including 16 major epigenetic clocks) and compared measurements taken before and after each intervention. “What we did was pretty unique.
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,” Sehgal said. The studies covered four broad categories: lifestyle changes, pharmacological treatments, over-the-counter supplements, and medical procedures.
Programs combining exercise with a healthy diet consistently lowered epigenetic age, regardless of whether the eating plan was Mediterranean, low-carb, or low-fat. Prescription drugs produced the largest decreases. The strongest results appeared with metformin and semaglutide, which are used for metabolic control and weight management, and anti-TNF treatments, which block an immune system protein involved in harmful inflammation. (TNF, or tumor necrosis factor, is an immune system protein that helps fight inflammation-related injury.) By comparison, the supplements and certain medical procedures included in the analysis did not significantly reduce epigenetic age. Newer biological age clocks also detected intervention-related changes more effectively than older models
