Weight-Loss Jabs May Slow Biological Ageing, Early Mouse and Human Data Suggest

Twenty months is old for a laboratory mouse. It was at that age that researchers began giving female mice injections of semaglutide, and they kept doing so for the rest of the animals' lives. The mice lived 92 days longer than expected, a 12 per cent gain over the typical median lifespan of 742 days. The work was published recently in Nature, and it has some scientists cautiously asking whether GLP-1 drugs, best known for treating diabetes and obesity, might touch the biology of ageing itself.

The injected mice also looked healthier at the cellular level. They showed less inflammation, fewer senescent cells, and mitochondria that worked better. Mitochondria are the structures that help cells turn nutrients and oxygen into energy. The mice also grew more new cells in brain regions involved in learning and memory.

Prof Richard Faragher, a biological gerontologist at the University of Brighton, called the drop in senescent cells significant. He described them as cells that deliberately drive inflammation, signalling to attract immune cells that will destroy them. The trouble, he said, is that the immune system is made of cells too, and it ages. In a teenager a senescent cell is quickly cleared; in an older person the response is more like being put on hold at a busy dentist's office. Damage accumulates as a result: wrinkles in skin, cardiovascular disease in blood vessels, cognitive impairment in the brain.

There was an obvious objection. Semaglutide suppresses appetite, so the benefits might simply reflect mice eating less. The researchers ran a separate five-month study with new mice. Semaglutide had cut food intake by about 24 per cent, so they restricted a comparison group's calories by the same amount. Both groups lost comparable body weight and fat mass and performed similarly on treadmills. The semaglutide mice still did better on spatial memory, glucose control and exploratory behaviour. Faragher said it is increasingly clear that GLP-1 receptor agonists affect life expectancy independently of their effect on body mass.

A human parallel comes from an analysis published earlier this year by researchers including Dr Grace McComsey, an HIV researcher. It drew on a 32-week randomised, double-blind, placebo-controlled trial of 84 adults living with HIV, a group that tends to age faster biologically. All had HIV-associated lipohypertrophy, an abnormal buildup of fat, and received weekly semaglutide or a placebo. The original trial asked whether the drug reduced that fat. Researchers later returned to the data and analysed ageing.

Compared with placebo, the semaglutide group showed a nine per cent slower pace of biological ageing. They also showed significant changes in markers tied to all-cause mortality risk, and positive signals in blood-based measures of inflammation and of brain and heart ageing. McComsey said the drug appeared to reduce the accumulation of age-related changes in DNA, which suggests it may affect ageing biology rather than merely treating disease. She said the mouse findings mirrored several of the human observations: improved cognition, decreased inflammation and reduced ageing biomarkers.

She was careful to say these drugs are not miracles. About a third of participants did not reach the prespecified threshold of at least five per cent weight loss, and she said researchers need to understand why. Rare side effects include optic neuropathy and encephalitis. A common one is significant muscle loss, and she urged people to exercise while taking GLP-1s because the loss may not be easily reversed.

The evidence remains thin. One group of female mice and a relatively small post-hoc analysis in people with a condition that speeds ageing cannot support firm conclusions. Testing in more varied ageing populations is needed. Faragher argues that governments should take the drugs seriously now, given the implications for pension ages and health systems, and called this the greatest change in population health since penicillin.

He also framed it personally. His father, who died a few years ago, always wanted a ten-day cruise to Egypt; a terrorist attack cancelled the first attempt and his mother's hospitalisation ended the second. Two extra weeks of healthy life, Faragher said, would have been enough for him to tick off that one item.