Semaglutide, the active ingredient in Ozempic and Wegovy, may slow some molecular signs linked to biological aging, according to a randomized, placebo-controlled clinical study involving adults with HIV associated lipohypertrophy.
The study, published in Nature Communications, examined whether the GLP-1 drug affected epigenetic clocks, which estimate biological aging by tracking DNA methylation patterns. The work analyzed data from a previous clinical trial of 108 adults, while the epigenetic analysis included paired DNA methylation data from 84 participants.
The original trial tested weekly semaglutide injections against placebo over 32 weeks in adults with HIV associated lipohypertrophy, a condition linked to excess abdominal fat.
Instead of focusing only on weight, blood sugar, or body fat, the new analysis looked at biological age through epigenetic clocks. These tools measure chemical changes in DNA that can reflect age-related changes before disease appears.
Participants treated with semaglutide showed slower biological aging patterns across several epigenetic clocks linked to inflammation and major body systems, including the brain, heart, blood, kidney, liver, and metabolic health.
The pace of biological aging slowed by 9% on the DunedinPACE clock. Semaglutide also reduced measures linked to age-related disease and all-cause mortality risk on the PCGrimAge clock.
Researchers noted that the findings are early and do not show that semaglutide reverses aging or makes people younger. Larger studies are needed to confirm whether GLP-1 drugs can produce durable effects on aging biology.
People living with HIV can experience faster biological aging even when the virus is controlled with modern antiretroviral therapy. Chronic inflammation, immune activation, and metabolic stress are believed to contribute to that process.
Semaglutide may affect aging-related pathways by lowering inflammation, reducing metabolic stress, and decreasing visceral and ectopic fat around the abdomen and internal organs. Those changes may reduce signals that contribute to faster aging.
A related pilot study in npj Aging examined 24 weeks of semaglutide treatment in 41 people with HIV and metabolic dysfunction-associated steatotic liver disease, also known as MASLD or fatty liver disease.
In that study, 41.5% of participants showed a reduced pace of biological aging on the DunedinPACE clock and also had greater reductions in liver fat. A rise in telomere length was linked with better gait speed, while PCGrimAge changes suggested early signals tied to mortality risk markers.
The findings add to evidence that GLP-1 drugs may influence biological pathways beyond weight loss and blood sugar control. However, the main trial focused on people with HIV associated lipohypertrophy, so the results may not apply directly to the wider population.
Future trials will need to test whether the effect persists over time, whether different GLP-1 drugs produce different results, and whether lifestyle changes such as diet, exercise, and sleep optimization can strengthen the impact on aging markers.
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