People living with HIV may experience accelerated biological aging compared with people without HIV. Even when HIV is well controlled with antiretroviral therapy, ongoing inflammation and immune system activation can contribute to earlier development of age-related conditions, such as cardiovascular disease, osteoporosis, and frailty.
Those living with HIV may also experience lipohypertrophy, which is the accumulation of fat in certain areas of the body. It is thought to result from a combination of HIV infection, chronic inflammation, and some antiretroviral treatments.
Semaglutide is the active ingredient in glucagon-like peptide-1 (GLP-1) receptor agonist drugs, such as Ozempic and Wegovy. This medication can lead to significant weight loss, particularly by reducing body fat.
Originally investigating whether semaglutide could reduce excess fat in those with HIV-associated lipohypertrophy, a post hoc analysis suggests that the GLP-1 drug may not only reduce fat accumulation but may also slow biological aging.
The new study, published in Nature Communications, found that adults living with HIV who received semaglutide showed slower progression of several molecular markers linked to biological aging compared with those who received a placebo.
However, researchers caution that the findings do not mean the drug reverses aging, but could influence pathways involved in age-related disease.
A collaborative research team analyzed data from a randomized, placebo-controlled clinical trial involving 84 adults with HIV-associated lipohypertrophy. Participants received either weekly semaglutide injections or placebo injections for 32 weeks.
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As people living with HIV often experience accelerated biological aging, the researchers suggest this population is particularly useful for studying interventions that target age-related mechanisms and may provide insights that extend beyond this specific group.
To assess biological aging, researchers used several epigenetic clocks. These are tools that estimate biological age by measuring DNA methylation patterns, which are chemical modifications that affect gene activity without altering the genetic code itself.
Compared with participants who received a placebo, those treated with semaglutide showed slower biological aging in inflammation, brain, and heart measures.
Additionally, those taking semaglutide also showed a 9% reduction in the pace of biological aging, as measured by the DunedinPACE clock, and significant improvements in markers linked to all-cause mortality risk and age-related disease, as measured by the PCGrimAge clock.
First study author Michael Corley, PhD, associate professor of medicine in the Division of Geriatrics, Gerontology & Palliative Care at UC San Diego School of Medicine and the Stein Institute for Research on Aging, spoke to Medical News Today about the study findings.
“The message I’d emphasize is one of cautious optimism: we are not saying semaglutide reverses aging or makes anyone younger. What we are seeing is a signal that it may slow some of the biology underlying age-related disease, and that signal now deserves to be tested directly in larger trials,” Corley told us.
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“The key point is that this is the first randomized, placebo-controlled clinical evidence that a GLP-1 receptor agonist may slow the biological processes associated with aging in humans.”
– Michael Corley, PhD
“Using multiple epigenetic clocks, we saw a broad pattern of slower biological aging in participants treated with semaglutide compared with placebo, including a 9% slowing in the pace of aging measured by DunedinPACE and a significant effect on PCGrimAge, which tracks processes linked to all-cause mortality and age-related disease,” the researcher detailed.
GLP-1 drugs, such as semaglutide, are often prescribed for managing obesity and type 2 diabetes, and are known to lower blood sugar, reduce body weight, and decrease cardiovascular risk.
The researchers suggest that several mechanisms could potentially explain the apparent anti-aging effects of GLP-1 drugs.
“What stood out to me was less the size of any single effect than the consistency of the pattern across clocks tied to different organ systems including inflammation, blood, brain, heart, kidney, liver and metabolic health,” Corley told MNT.
“Because people with HIV often experience accelerated aging even when the virus is well controlled, this was a population where we might expect a metabolic intervention to register a measurable signal, so the direction was plausible. The breadth of the response across so many independent measures was the more striking part,” he noted.
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One possibility lies in the anti-inflammatory properties of semaglutide, which can reduce chronic inflammation and metabolic stress. Both of these factors are considered major drivers of biological aging.
GLP-1 drugs also reduce visceral fat, the metabolically active fat that accumulates around internal organs and contributes to inflammation.
Emerging evidence also suggests GLP-1 drugs may influence cellular function in multiple organs, potentially producing widespread effects on aging-related biological pathways.
“[reductions in inflammation or visceral fat] are very likely two of the potential central drivers,” Corley explained to MNT. “By reducing inflammation and metabolic stress, GLP-1 drugs lower chronic immune activation, which is a primary contributor to accelerated aging in people with HIV.”
“They also reduce the visceral and ectopic fat that accumulates around the abdomen and organs, which may quiet the inflammatory and metabolic signals that promote aging,” he added.
“Emerging data also suggest these drugs may reprogram certain cells across different organs, and that could help explain why we see effects across multiple aging clocks rather than in just one system,” Corley told us.
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The findings build on a separate pilot study published in npj Aging, which examined semaglutide treatment in people living with HIV who also had metabolic dysfunction-associated steatotic liver disease(MASLD), previously known as fatty liver disease.
In that study, researchers found that semaglutide reduced the pace of biological aging in 42% of participants, slowed aging-related mortality risk markers in 34% of participants, and increased telomere-length markers in nearly half of participants, alongside improvements in physical function.
Although the pilot study was smaller, its results point in a similar direction, suggesting that GLP-1 therapies may affect biological aging pathways.
However, while the results of both studies are promising, the researchers stress that the findings should be interpreted cautiously.
As the studies focused specifically on adults living with HIV, the results may not automatically apply to broader populations. In addition, researchers measured biological aging using molecular biomarkers rather than direct clinical outcomes such as lifespan or rates of age-related disease.
Thus, larger and longer-term clinical trials will be necessary to determine whether the observed changes translate into meaningful health benefits and whether similar effects occur in people without HIV.
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While more research is needed before considering semaglutide as an anti-aging therapy, these findings raise the possibility that GLP-1 medications could one day play a role in strategies designed to extend healthspan.
“Many of the biological processes we study in HIV are also central to aging in the general population and they simply tend to emerge earlier or more prominently in this community, which makes it a useful window for identifying interventions that could improve healthspan more broadly,” Corley told MNT.
“So it is reasonable to hypothesize that similar effects could occur in people without HIV, but that has to be confirmed in dedicated trials,” he suggested.
“Whether GLP-1–based therapies eventually fit into healthy-aging strategies will depend on larger studies establishing how durable the effects are, optimal dosing and duration, and whether benefits are enhanced when combined with diet, exercise and sleep,” the researcher noted.
“With newer GLP-1 therapies emerging, the field has a real opportunity to test which drugs in this class have distinct effects on aging biology and which patients benefit most,” he concluded.
