Yale Study Reveals Which Anti-Aging Treatments Actually Reduce Biological Age

Yale scientists have identified specific prescription medications and lifestyle changes that can reduce biological age, according to a study published in Nature Medicine.

The research, led by Raghav Sehgal, an associate research scientist in psychiatry at the Yale School of Medicine, suggests that while certain interventions show measurable effects on DNA-based aging markers, many popular over-the-counter supplements do not. This distinction is critical as the “longevity” market continues to expand, often blurring the line between clinically backed interventions and unproven wellness products.

“For the first time we’ve shown that certain therapies have measurable impacts,” Sehgal told Science Daily. “This wasn’t previously possible, because we didn’t have enough data to say these biomarkers are consistently responsive to these interventions.”

The study moves from focusing on individual diseases like cancer or diabetes toward investigating the underlying biological processes of aging itself. By using advanced computational biology, the team sought to determine if the aging process is more flexible than previously assumed.

Researchers use DNA methylation to measure biological age

To measure aging, the researchers relied on epigenetic clocks, which are blood-based tests that analyze chemical patterns attached to DNA. Specifically, they looked at DNA methylation—the presence of methyl groups that act as chemical tags on the genome. These tags change predictably as a person grows older, providing a window into biological age that can differ significantly from a person’s chronological age.

The Yale team analyzed data from 51 clinical studies, examining more than 110 DNA methylation biomarkers, including 16 major epigenetic clocks. This wide-ranging approach allowed them to compare measurements taken before and after various interventions to see which ones actually moved the needle on biological aging markers.

The researchers categorized the interventions into four distinct groups to compare their effectiveness:

Intervention Category	Observed Impact on Biological Age
Prescription Medications	Strongest reductions observed (e.g., metformin, semaglutide, anti-TNF therapies)
Lifestyle Modifications	Consistent reductions through diet and exercise
Over-the-Counter Supplements	Showed little evidence of producing meaningful effects
Medical Procedures	Generally failed to produce measurable reductions

Lifestyle changes and specific prescriptions reduce epigenetic age

The data revealed that lifestyle changes—specifically the combination of regular physical activity and nutritious eating plans like the Mediterranean, low-fat, or low-carb diets—consistently reduced epigenetic age. However, the most significant reductions were linked to specific pharmaceutical treatments.

Metformin and semaglutide, both widely used for metabolic regulation and weight management, were among the most effective. Anti-TNF therapies, which target proteins involved in the body's inflammatory response, showed promise in influencing aging biomarkers.

Conversely, the study provided a reality check for the supplement industry. The over-the-counter products examined in the research generally failed to produce measurable changes in the epigenetic clocks used by the team. This suggests a gap between commercial marketing and biological reality.

The findings also noted a nuance in how aging is measured: individuals living with existing diseases generally experienced larger changes in their aging biomarkers than healthy participants did.

The gap between biomarkers and longevity

While the ability to measure biological age through blood tests could revolutionize how we study aging, experts are urging caution regarding the ultimate goal: living longer. A reduction in a chemical marker on the DNA does not automatically translate to a longer lifespan or the prevention of disease.

“And most importantly—what does the change mean for our long-term risk of age-related disease and functional decline?” Albert Higgins-Chen, an assistant professor of psychiatry at the Yale School of Medicine and senior author of the study, told Science Daily.

There are several unanswered questions that remain at the center of the debate. Researchers have yet to confirm if the changes in biological age are directly caused by the treatments or if they are influenced by external variables. It is also unknown how long these effects last once a treatment is stopped, or if these changes lead to meaningful improvements in functional health.

If these biomarkers are eventually validated to predict long-term health, the implications for medical research are massive. Instead of waiting decades for the results of clinical trials to see if a drug extends life, scientists could potentially use these blood tests to see if a treatment is working within months.

“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.

The next phase of research will focus on testing these findings across larger, more diverse populations to see how these treatments perform across different backgrounds and health conditions.