The growing popularity of GLP-1 medications such as Ozempic, Wegovy, and Rybelsus is largely due to 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 those drugs, may also help slow some of the biological processes associated with aging.
Published in Nature CommunicationsThe study provides the first randomized, placebo-controlled evidence in humans that semaglutide can slow the accumulation of DNA markers related to biological aging in adults living with HIV.
Biological aging markers delayed with semaglutide
Scientists at the University of California, San Diego and collaborating institutions examined data from a previous clinical trial involving 108 adults with HIV-associated lipohypertrophy, a condition that causes excess fat to accumulate around the abdomen. About half of the participants received weekly injections of semaglutide, while the rest received a placebo for comparison.
To assess aging, the researchers relied on several “epigenetic clocks.” These tools estimate biological age by measuring DNA methylation, a pattern of chemical tags that influences how genes are turned on or off without changing the DNA sequence. Changes in these markers can provide information about whether the body’s cells appear to age faster or slower than expected.
People living with HIV often experience accelerated biological aging, even when the virus is well controlled with modern antiretroviral therapy, explained first author Michael Corley, PhD, associate professor at UC San Diego School of Medicine and the Stein Institute for Research on Aging.
Compared to participants receiving placebo injections, those treated with semaglutide showed:
- Slower biological aging through multiple epigenetic clocks linked to inflammation and blood, brain, heart, kidney, liver and metabolism health.
- A 9% slower rate of biological aging according to the DunedinPACE epigenetic clock.
- A significant slowing of biological processes related to age-related diseases and the risk of all-cause mortality, as measured by the PCGrimAge epigenetic clock.
Why might GLP-1 drugs affect aging?
Researchers believe that semaglutide may influence aging through several interconnected pathways.
GLP-1 medications reduce inflammation and improve metabolic health, which may decrease chronic immune activation, a major driver of accelerated aging in people with HIV. They also reduce visceral fatfat stored deeply around internal organs, as well as ectopic fat that accumulates in places where fat does not normally belong. Lower levels of these harmful fat deposits can reduce inflammatory signals that contribute to aging throughout the body.
“Emerging data also suggest that GLP-1 drugs can reprogram certain cells in different organs, which could help explain why we see effects on multiple aging clocks,” Corley said.
Findings could extend beyond people with HIV
Although the research focused on people with HIV-associated lipohypertrophy, the researchers believe the findings could have broader implications.
“Many of the biological processes we study in HIV are also critical to aging in the general population,” Corley said. “Because these processes may emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that can improve health more broadly.”
Life expectancy refers to the number of years a person remains healthy and free of major age-related diseases, rather than simply how long they live.
A related study found more signs of slower aging
The team also pointed to a pilot study published last month in agingwhich examined semaglutide treatment for 24 weeks in people with HIV and metabolic dysfunction-associated steatotic liver disease (MASLD), also known as fatty liver disease.
That study found:
- Biological aging slowed in 42% of participants, according to the DunedinPACE epigenetic clock. Those individuals also experienced greater reductions in liver fat than participants whose biological aging was accelerated.
- Aging linked to all-cause mortality risk slowed in 34% of participants, according to the PCGrimAge epigenetic clock.
- Nearly 49% of participants showed longer telomeres, the protective DNA caps at the ends of chromosomes, as measured by the PCDNAmTL epigenetic clock. Those participants also tended to walk faster after treatment, suggesting improvements in physical function.
Together, the two studies add to growing evidence that GLP-1 drugs can affect biological pathways involved in aging.
Scientists urge caution
Despite the promising findings, the researchers emphasize that semaglutide is not an anti-aging drug.
“We’re not saying that semaglutide reverses aging or makes people younger,” Corley said. “What we are seeing is a sign that it may slow some of the biological processes associated with aging. With new GLP-1-based therapies now emerging, the field has the opportunity to test whether different drugs in this class have different effects on the biology of aging and identify which patients may benefit the most.”
Much larger clinical trials will be needed to confirm the results, determine how long the benefits last, and identify the most effective treatment regimens for both people with HIV and the general population. The researchers also want to investigate whether combining GLP-1 drugs with healthy habits such as diet, exercise, and quality sleep could produce even greater effects on biological aging.
Looking ahead, the Stein Institute for Aging Research hopes to use these findings to develop personalized “aging dashboards” based on epigenetic clocks. The goal is to help doctors monitor biological aging more precisely and design individualized treatments that target the underlying causes of age-related diseases.
He Nature Communications 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. The related npj Aging study 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 scientific advisor to TruDiagnostic.