Semaglutide extends lifespan and slows physiological aging in healthy mice

A National Institutes of Health (NIH)-funded study has shown that the GLP-1 drug semaglutide extended lifespan in older, healthy mice by tempering the detrimental effects of aging. Researchers at the University of California, Berkeley directly compared the effects of the treatment to those of reduced food intake. They found that the drug mimicked the anti-aging benefits of calorie restriction, conferring even greater benefits in some areas.

While GLP-1s have been found to delay the onset of many age-related diseases in animals, this new study in healthy older mice offers evidence that these drugs may slow physiological aging itself, a notion that could potentially tie the widespread benefits of GLP-1s to a common source.

"Most chronic diseases are deeply rooted in the aging process. If GLP-1 agonists do indeed slow it down, then a wide range of clinical benefits is exactly what you'd expect to see," said Rafael de Cabo, Ph.D., a senior investigator at the NIH's National Institute on Aging (NIA), and author of a commentary on the new study.

To understand the impact of GLP-1s at a time when the effects of aging are most pronounced, the study authors, led by Danica Chen, Ph.D., administered semaglutide to 20-month-old female mice for three months.

Compared with a control group, mice treated with the drug showed improved muscle and cognitive function. Gene expression analysis showed that several hallmarks of natural aging, such as increased inflammation and reduced regenerative capacity, were reduced in treated animals.

Another group of mice treated until the end of life had a median lifespan nearly 100 days longer than that of untreated mice.

The authors then compared semaglutide with calorie restriction to see whether its benefits were simply due to reduced food intake or something else.

Over five months, scientists administered semaglutide to one group of 20-month-old female mice, while another group received a 24% calorie-restricted diet that matched the treated animals' feeding pattern. The authors drew numerous parallels between the two groups, with most physiological measurements remaining stable. However, semaglutide-treated mice surpassed baseline levels in exploratory behavior, spatial memory, and blood-sugar maintenance. The groups also differed in metabolic rate, which was reduced in the calorie-restricted animals but largely unchanged in the semaglutide-treated mice.

These differences point to the possibility that GLP-1 drugs tap into a biological pathway independent of calorie restriction. Uncovering this potential route and the benefits that may specifically stem from it is an important direction for future research into the development of longevity-enhancing interventions." 

Danica Chen, Ph.D., corresponding author of the study and professor of metabolic biology and nutrition at UC Berkeley

While these findings may guide future research, they do not imply that similar results could be achieved immediately in humans. Additional clinical studies, such as the recent post-hoc analysis of the SLIM LIVER trial, will be necessary to determine the clinical efficacy of GLP-1s on longevity in human patients.

Future clinical investigations may also explore benefits in healthy aged individuals, Chen explained, which would greatly broaden the application of GLP-1s.