Semaglutide shows signs of slowing some aging markers in HIV trial
UC San Diego researchers reported that semaglutide slowed epigenetic aging signals in a randomized trial of 108 adults living with HIV.
By Priya Raghavan · Science Reporter
3 min read
Semaglutide, the drug ingredient used in Ozempic, Wegovy and Rybelsus, slowed several molecular measures tied to aging in a clinical trial of adults with HIV, according to researchers at the University of California San Diego. The findings add a new line of inquiry for GLP-1 drugs, though the scientists said the results do not show that the medicine reverses aging or should be used as an anti-aging treatment.
The study, published in Nature Communications, analyzed data from 108 adults with HIV-associated lipohypertrophy, a condition marked by excess fat around the abdomen. About half of the participants received weekly semaglutide injections, while the rest received placebo injections, UC San Diego said.
Researchers assessed biological aging using epigenetic clocks, tools that estimate aging-related changes by measuring DNA methylation. DNA methylation involves chemical tags on DNA that affect gene activity without changing the genetic code itself.
According to the research team, participants treated with semaglutide showed slower aging signals across several clocks linked to inflammation and to the health of organs and systems including the blood, brain, heart, kidneys, liver and metabolism. One measure, the DunedinPACE clock, indicated a 9% slower pace of biological aging among those who received semaglutide compared with placebo, the researchers reported.
The team also found slower activity on PCGrimAge, an epigenetic measure associated with age-related disease and all-cause mortality risk. The study authors described the work as the first randomized, placebo-controlled human evidence that semaglutide may affect epigenetic signs of aging in adults living with HIV.
Why HIV was part of the study
Michael Corley, an associate professor at the UC San Diego School of Medicine and the Stein Institute for Research on Aging, said people with HIV can show accelerated biological aging even when antiretroviral treatment keeps the virus under control. Corley was the study’s first author.
The researchers said semaglutide could affect aging-related biology through its known effects on inflammation, metabolism and fat distribution. GLP-1 drugs can reduce visceral fat, which surrounds internal organs, and ectopic fat, which builds up in areas where fat is not normally stored; the team said lowering those fat deposits may reduce inflammatory signals linked to aging.
Corley also said emerging evidence suggests GLP-1 drugs may alter the behavior of some cells in multiple organs, which could help explain why different epigenetic clocks changed in the study. The researchers said processes seen in HIV may also be relevant to aging in the wider population, because some of the same inflammatory and metabolic pathways are involved.
Related pilot study found similar signals
The UC San Diego team also cited a pilot study published in npj Aging that examined 24 weeks of semaglutide treatment in people with HIV and metabolic dysfunction-associated steatotic liver disease, also known as fatty liver disease. In that study, the researchers reported slower DunedinPACE aging in 42% of participants, and those participants had larger reductions in liver fat than those whose aging measure accelerated.
The pilot study also found slower PCGrimAge signals in 34% of participants. Nearly 49% showed longer telomere-related measures using the PCDNAmTL epigenetic clock, and those participants tended to walk faster after treatment, according to the researchers.
Researchers urge restraint
Corley said the findings should not be read as proof that semaglutide makes people younger. He said the results point to a signal that the drug may slow some biological processes associated with aging.
UC San Diego said larger trials will be needed to confirm the findings, test how long any effect lasts and determine which patients may benefit. Researchers also want to study whether GLP-1 drugs combined with diet, exercise and sleep improvements have stronger effects on aging markers.
The Nature Communications study was supported in part by the National Institutes of Health and the James B. Pendleton Charitable Trust, according to UC San Diego. The university said Corley serves as a scientific adviser for TruDiagnostic.
This story draws on original reporting from ScienceDaily.