Beyond the widespread attention GLP-1 drugs are receiving for treating obesity, lowering blood sugar and decreasing the risk of cardiovascular disease, emerging research is investigating their other potential impacts — including their effects on aging.
Now, a new study provides the first randomized, placebo-controlled clinical evidence that semaglutide, a widely used GLP-1 drug, slows down the accumulation of biological aging markers in the DNA of adults with HIV. The study is published in Nature Communications.
Researchers at the University of California, San Diego and several partner institutions analyzed data from a previously published clinical trial of 108 adults with HIV‑associated lipohypertrophy, a condition in which excess fat builds up around the abdomen. About half of the participants received weekly injections of semaglutide, with the rest receiving placebo injections.
The team used a set of biological “epigenetic clocks” to track cellular aging over the 32-week treatment period. These clocks detect DNA methylation, chemical marks on DNA that help regulate how genes are turned on or off without changing the genetic sequence itself. By measuring changes in these marks, the team could assess whether the treatment was associated with a slower or faster biological aging pattern.
People with HIV often experience accelerated aging, even if it is well-controlled with antiretroviral therapy, according to first author Michael Corley, Ph.D., associate professor at UC San Diego School of Medicine and the Stein Institute for Research on Aging. However, the study found compared to the placebo group:
Participants treated with semaglutide exhibited a broad pattern of slower biological aging across epigenetic clocks linked to inflammation and blood, brain, heart, kidney, liver and metabolic health.
The drug slowed the pace of biological aging by 9 %, as measured by the DunedinPACE epigenetic clock.
The drug significantly slowed biological processes associated with the risk of all‑cause mortality and age-related disease, as measured by the PCGrimAge epigenetic clock.
Research suggests there are several mechanisms by which semaglutide may influence biological aging. By reducing inflammation and metabolic stress, GLP-1 drugs decreased chronic immune activation, a primary driver of accelerated aging in people with HIV. They also reduce visceral and ectopic fat that accumulates around the abdomen and organs, which may help curb the inflammatory and metabolic signals that promote aging.
“Emerging data also suggest that GLP-1 drugs may reprogram certain cells in different organs, which could help explain why we see effects across multiple aging clocks,” said Corley.
While the study focused on people with HIV‑associated lipohypertrophy, Corley says it may also offer lessons for the wider population.
“Many of the biological processes we study in HIV are also central to aging in the general population,” he said. “Because these processes can emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that may improve healthspan more broadly.”