The growing popularity of GLP-1 therapeutics such as Ozempic, Wegovy, and Rybelsus is primarily driven by their ability to help people lose weight, improve blood sugar control, and reduce the risk of cardiovascular disease. Now, researchers have discovered another possible benefit. A new clinical trial suggests that semaglutide, the active ingredient in these drugs, may help slow some of the biological processes associated with aging.
Published in nature communicationsthis study provides the first randomized, placebo-controlled evidence in humans that semaglutide may slow the accumulation of DNA markers associated with biological aging in adults living with HIV.
Semaglutide is a marker that slows biological aging
Scientists at the University of California, San Diego and partner institutions examined data from an earlier clinical trial of 108 adults with HIV-related lipohypertrophy, a condition in which excess fat accumulates around the abdomen. Approximately half of the participants received weekly semaglutide injections, and the remaining participants received a placebo for comparison.
To assess aging, researchers relied on several “epigenetic clocks.” These tools estimate biological age by measuring DNA methylation, the pattern of chemical tags that affect how genes are switched on and off without changing the DNA sequence itself. Changes in these markers can provide insight into whether the body’s cells appear to be aging faster or more slowly than expected.
People with HIV often experience accelerated biological aging, even when the virus is well controlled with modern antiretroviral therapy, explained lead author Dr. Michael Corey, associate professor at the University of California, San Diego School of Medicine and the Stein Institute on Aging.
Compared to participants who received a placebo injection, participants treated with semaglutide had the following results:
- Delaying biological aging across multiple epigenetic clocks related to inflammation and blood, brain, heart, kidney, liver, and metabolic health.
- DunedinPACE Slows the pace of biological aging by 9% based on the epigenetic clock.
- Significant slowing of biological processes, as measured by the PCGrimAge epigenetic clock, is associated with age-related diseases and all-cause mortality risk.
Why do GLP-1 drugs affect aging?
Researchers believe that semaglutide may affect aging through several interrelated pathways.
GLP-1 drugs reduce inflammation and improve metabolic health. This may reduce chronic immune activation, which is one of the main factors contributing to accelerated aging in HIV-infected individuals. Also, visceral fatfat that accumulates deep around internal organs, and ectopic fat that accumulates in places where fat normally does not exist. Reducing the levels of these harmful fat deposits may reduce inflammatory signals that contribute to aging throughout the body.
“Emerging data also suggest that GLP-1 drugs may reprogram specific cells in different organs, which may help explain why effects are seen across multiple aging clocks,” Corey said.
Findings could spread beyond people living with HIV
Although the study focused on patients with HIV-associated lipohypertrophy, the researchers believe their findings may have broader implications.
“Many of the biological processes we study in relation to HIV are also central to aging in the general population,” Professor Corley said. “These processes may appear earlier or be more pronounced in people with HIV, so this community can help identify interventions that have the potential to improve healthspan more broadly.”
Healthy life expectancy does not simply mean a long lifespan, but refers to the number of years a person is healthy and free from major age-related diseases.
Related research reveals more signs of slowing aging
The research team also pointed to a pilot study published last month. npj agingThis study investigated 24 weeks of semaglutide treatment in patients with HIV and metabolic dysfunction-associated fatty liver disease (MASLD), also known as fatty liver disease.
The study found:
- Based on the DunedinPACE epigenetic clock, 42% of participants experienced slower biological aging. Those people also experienced greater reductions in liver fat than participants with accelerated biological aging.
- According to the PCGrimAge epigenetic clock, aging associated with all-cause mortality risk slowed in 34% of participants.
- Nearly 49% of participants had longer telomeres, the protective DNA caps at the ends of chromosomes, as measured by the PCDNAmTL epigenetic clock. These participants also tended to walk faster after treatment, suggesting improved physical function.
Together, the two studies add to growing evidence that GLP-1 drugs can influence biological pathways involved in aging.
Scientists urge caution
Despite the promising findings, researchers stress that semaglutide is not an anti-aging drug.
“We’re not saying semaglutide reverses aging or rejuvenates you,” Corey said. “What we’re seeing is a signal that it may slow down some of the biological processes associated with aging. Now that new GLP-1-based therapies are emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on the biology of aging and identify which patients will benefit most.”
Larger clinical trials will be needed to confirm the results, determine how long the effects last, and identify the most effective treatment schedules for both people with HIV and the broader population. Researchers also want to investigate whether combining GLP-1 drugs with healthy habits such as diet, exercise, and quality sleep can have an even greater impact on biological aging.
Looking ahead, the Stein Institute on Aging hopes to use these findings to develop a personalized “aging dashboard” based on the epigenetic clock. The goal is to enable clinicians to more accurately monitor biological aging and design personalized treatments that target the underlying causes of age-related diseases.
of nature communications This research was funded in part by the National Institutes of Health (grants P30 AI036214, R01DK121619 and UM1TR004528) and the James B. Pendleton Charitable Trust. Associated npj aging research was also supported 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 to TruDiagnostic.
