Glucagon-like peptide-1 (GLP-1) receptor agonist medications have gained widespread attention for effectively treating obesity, lowering blood sugar and decreasing the risk of cardiovascular disease. Some researchers have proposed that these drugs may also influence the biology of aging, but direct evidence in humans has remained limited. 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, PhD, 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."
In a related pilot study published in npj Aging last month, Corley and another team of researchers found that taking semaglutide for 24 weeks:
- Reduced the rate of biological aging for 42% of participants with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD) — also known as fatty liver disease — as measured by the DunedinPACE epigenetic clock. Those participants also had a greater reduction in liver fat compared with participants whose pace of aging sped up.
- Slowed aging associated with the risk of all‑cause mortality in 34% of participants as measured by the PCGrimAge epigenetic clock.
- Increased the length of telomeres — repetitive DNA sequences at the ends of chromosomes that protect genetic material — in nearly 49 % of participants as measured by the PCDNAmTL epigenetic clock. Those participants also tended to walk faster after treatment, suggesting better physical function.
Together, these studies add to growing evidence that GLP-1 drugs may influence pathways involved in biological aging.
"We are not saying that semaglutide reverses aging or makes people younger," said Corley. "What we are seeing is a signal that it may slow some of the biological processes associated with aging. With newer GLP-1–based therapies now emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on aging biology and to identify which patients may benefit most."
Larger clinical trials are needed to confirm the findings, determine how long treatment effects last, and establish optimal dosing and treatment duration for both people with HIV and the broader population. Future studies will also be needed to test whether the effects of GLP-1 effects on aging biology are enhanced when combined with lifestyle interventions such as diet, exercise and sleep optimization.
The Stein Institute for Research on Aging plans to translate these results into individualized "aging dashboards" to track biological aging with epigenetic clocks, enabling clinicians to design personalized therapies that target the underlying mechanisms of aging and help prevent age‑related diseases.
Additional co-authors on the Nature Communications study include: Alina P. S. Pang at UC San Diego; Varun Dwaraka and Ryan Smith at TruDiagnostic; Danielle Labbato and Grace A. McComsey at University Hospitals Cleveland Medical Center; Allison Ross Eckard at the Medical University of South Carolina; and Grace A. McComsey at Case Western Reserve University. The study was funded, in part, by the National Institutes of Health (grants P30 AI036214, R01DK121619 and UM1TR004528) and the James B. Pendleton Charitable Trust.
Additional co-authors on the npj Aging study include: Alina P. S. Pang at UC San Diego; Douglas W. Kitch and Amy Kantor at Harvard T.H. Chan School of Public Health; Fred Sattler at University of Southern California Keck School of Medicine; Pablo F. Belaunzaran‑Zamudio at the National Institute of Allergy and Infectious Diseases. Todd T. Brown at Johns Hopkins University School of Medicine; Alan Landay at the University of Texas Medical Branch; Jordan E. Lake at UTHealth Houston; and Kristine M. Erlandson at University of Colorado Anschutz Medical Campus. The study was funded, in part, by the National Institutes of Health (grants P30 AI036214, UM1 AI068634, UM1 AI068636, UM1 AI106701) and the James B. Pendleton Charitable Trust.
Corley serves as a scientific advisor for TruDiagnostic.
