A widely prescribed class of weight-loss and diabetes medications may be doing more than improving metabolic health.
Drugs such as Ozempic and Wegovy have transformed the treatment of obesity and type 2 diabetes, helping millions lose weight and improve metabolic health. But scientists are increasingly uncovering effects that extend far beyond the scale. Research has linked GLP-1 medications to lower risks of cardiovascular disease, kidney disease, and even some neurodegenerative disorders. Now, a new clinical study suggests they may also influence one of medicine’s most intriguing frontiers: the biological processes that drive aging.
In a randomized, placebo-controlled trial, researchers found that semaglutide appeared to slow changes in DNA markers associated with biological aging in adults living with HIV. The study, published in Nature Communications, provides some of the strongest human evidence to date that a GLP-1 drug may affect molecular pathways tied to aging itself.
Looking Beyond Weight Loss
The study involved 108 adults with HIV-associated lipohypertrophy, a condition characterized by abnormal fat accumulation around the abdomen. Participants received either weekly semaglutide injections or placebo injections for 32 weeks.
Rather than focusing on traditional measures such as weight or blood sugar, the researchers examined biological age. To do this, they used a group of tools known as epigenetic clocks, which estimate how quickly the body is aging by analyzing DNA methylation patterns. These chemical modifications help regulate gene activity and can reveal age-related changes long before disease develops.
Epigenetic clocks have attracted growing interest because they often predict future health outcomes better than chronological age. Studies suggest that people whose biological age exceeds their actual age face a higher risk of disease and early death.
Signals of Slower Aging
People living with HIV frequently experience accelerated biological aging, even when the virus is well controlled with modern antiretroviral therapy. Researchers believe chronic inflammation and persistent immune system activation play important roles.
According to lead author Michael Corley, PhD, associate professor at UC San Diego School of Medicine and the Stein Institute for Research on Aging, semaglutide appeared to counter some of those effects.
Compared with participants who received a placebo, those treated with semaglutide showed slower aging patterns across multiple epigenetic clocks associated with inflammation and the health of several major organ systems, including the heart, brain, kidneys, liver, blood, and metabolic system.
Among the study’s most notable findings:
- The pace of biological aging slowed by 9% according to the DunedinPACE epigenetic clock.
- Biological processes linked to age-related disease and all-cause mortality risk were significantly reduced based on measurements from the PCGrimAge clock.
While the study was not designed to determine exactly how semaglutide produces these effects, researchers point to several possible mechanisms.
Researchers believe semaglutide may influence aging through several pathways. By reducing inflammation and metabolic stress, GLP-1 drugs may lower chronic immune activation, a major contributor to accelerated aging in people with HIV. The medications also reduce visceral and ectopic fat around the abdomen and internal organs, which may help decrease inflammatory and metabolic signals linked to 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.
Potential Relevance Beyond HIV
Although the study focused on people with HIV-associated lipohypertrophy, Corley believes the findings could have broader relevance.
“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, Corley and colleagues examined the effects of 24 weeks of semaglutide treatment in people with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD), also known as fatty liver disease.
The researchers found that:
- Biological aging slowed in 42% of participants, as measured by the DunedinPACE epigenetic clock. Those individuals also experienced greater reductions in liver fat than participants whose pace of aging increased.
- Aging-related markers associated with all-cause mortality risk slowed in 34% of participants, according to the PCGrimAge epigenetic clock.
- Telomere length increased in nearly 49% of participants, as measured by the PCDNAmTL epigenetic clock. These participants also tended to walk faster following treatment, suggesting improved physical function.
Together, the two studies add to a growing body of evidence suggesting that GLP-1 medications may affect biological pathways involved in aging.
More Research Needed
“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 will be needed to confirm these findings, determine how long the effects persist, and establish optimal dosing strategies and treatment durations for both people with HIV and the broader population.
Future research will also need to examine whether the effects of GLP-1 drugs on aging biology can be enhanced when combined with lifestyle interventions such as diet, exercise, and sleep optimization.
The Stein Institute for Research on Aging plans to translate these findings into individualized “aging dashboards” that use epigenetic clocks to track biological aging. Researchers hope these tools could eventually help clinicians design personalized therapies that target underlying aging mechanisms and reduce the risk of age-related disease.
References:
“Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy” by Michael J. Corley, Varun B. Dwaraka, Alina PS Pang, Danielle Labbato, Ryan Smith, Allison Ross Eckard and Grace A. McComsey, 19 May 2026, Nature Communications.
DOI: 10.1038/s41467-026-72861-3
“Pilot study of epigenetic aging and treatment response to semaglutide in the SLIM LIVER study” by Michael J. Corley, Alina P. S. Pang, Douglas W. Kitch, Amy Kantor, Fred Sattler, Pablo F. Belaunzaran-Zamudio, Todd T. Brown, Alan Landay, Jordan E. Lake and Kristine M. Erlandson, 21 April 2026, npj Aging.
DOI: 10.1038/s41514-026-00383-9
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.
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