September 2, 2026

expert reaction to GLP-1R-activating drug treatment slows ageing and extends lifespan in female mice

Scientists comment on a paper published in Nature exploring the effect of GLP-1R activating drug treatment on ageing and lifespan.

Dr Laura Sinclair, Lecturer in Healthcare, University of Exeter, said:

On the paper/wider implications:

“This paper is a very interesting and thorough study with lots of robust data.

Since GLP-RAs hit the mainstream, the biologists who specialise in ageing among us have been suspicious as to whether they might mimic the improvements in lifespan we see in calorie restriction. Calorie restriction is known to increase lifespan in lots of animal models, but it has had significant difficulty translating into a human therapy. We don’t yet know whether this is down to biological differences or simply that it is very difficult to restrict appetite to the necessary level to reproduce the same effects, or a combination of both. It’s intriguing that this study is showing differences between mice in the calorie restriction and GLP1-RA groups, leading to the conclusion that he GLP1-RAs had improved health benefits beyond the calorie restriction group.

The authors acknowledge there are a few big limitations to this study. 1. It’s in an animal model, 2. It’s only in females, and 3. The dosing started in “later life” and continued until death.

Animal models are deliberately not very genetically diverse, to enable detection of very small effects in experiments, however we know that a genetically diverse population can respond differently to foods and drugs. The animals in this study reportedly didn’t have any adverse effects, whereas, in humans, we do hear of people struggling with the side-effects of semaglutide (such as nausea), and we also observe those side-effects affecting men and women differently. We know that there are significant biological differences in tissues between mice and humans, such as our fat tissue, and between male and females.

For the lifespan part of this study, the mice received daily semaglutide from about 75% of their usual lifespan. In humans, with an average female life expectancy of 83 years in the UK, this would equate to starting treatment at about age 62 and continuing to be on the drug for life, which I could imagine being difficult for a lot of people.

This study provides some good, initial evidence in favour of our suspicions that GLP-RAs might mimic how calorie restriction affects lifespan and it goes further by finding improvements beyond calorie restriction. If the question is whether GLP1-RAs work for ageing for everyone, then many more research studies are needed. What we do know is that losing weight to be within a healthy range gives lots of health benefits, even if the individual later regains that weight. Naturally, the longer you maintain a healthy weight, the better for your biological ageing and risk of disease.

On the press release:

The press release is a fair assessment of the paper and science. As a senescence biologist, I would add that cellular senescence is not just “in which cells stop dividing”, but rather “in which cells stop dividing and are not functioning normally” as this is a core distinction of senescence versus other non-dividing cell states.”

Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:

“This is a well-conducted and interesting mouse study, but its findings fit with a growing body of evidence from placebo-controlled trials in humans. We already know from large meta-analyses that incretin-based therapies are linked to lower mortality risk in people with diabetes ^[1], with supportive evidence from the SELECT trial in people without diabetes. That some of these benefits may be driven by sustained reductions in calorie intake is biologically plausible and consistent with the wider literature. Eating less over long periods reduces the burden placed on multiple organs, including the heart, liver, pancreas and kidneys, and may have broader health benefits on the brain and other tissues as suggested in this new work. The key next step is to test these hypotheses in further randomised trials across a wider range of diseases, as recently suggested ^[2]. Animal studies are invaluable for generating insights, but ultimately we need robust human evidence, as not all findings in mice translate to people.”

[1] https://pubmed.ncbi.nlm.nih.gov/40156846/

[2] https://pubmed.ncbi.nlm.nih.gov/42660161/

Prof Tara Spires-Jones, Division Lead in the UK Dementia Research Institute at the University of Edinburgh, said:

“This study from scientists at the University of California, Berkely, showed that treating ageing female mice with the glucagon-like peptide-1 receptor (GLP-1R) agonist drug semaglutide prolonged their lifespan by around 11% and reduced several biological and cognitive hallmarks of ageing. This is an interesting and well-conducted study that adds important understanding of the biological effects of GLP-1R agonist drugs.  If these results from mice hold true in people, this is a promising hint that people taking GLP-1R agonists may have an age-slowing benefit as well as benefits to reducing diabetes and obesity. The good news for people who are not taking these drugs is that the boost in making new neurons in the brain and improvements in cognitive function that the scientists observed are likely due to the mice receiving semaglutide moving more than the control group as physical activity is known to boost brain health in similar ways without GLP-1R drugs. The main limitations of this study are that while well-conducted, this experiment was in mice and only female mice. Mice are quite different from humans in many ways including lifespan and the range of environmental exposures of laboratory animals is limited. Women and men also have different physiology in ageing including factors such as the menopause. It will be interesting in the future to determine whether these results hold true in male mice and ultimately in people taking these drugs.”

* ‘Late-life semaglutide treatment slows ageing and extends lifespan in female mice’ by Yufan Feng et al. was  published in Nature on Wednesday 2nd September.

DOI: 10.1038/s41586-026-10940-7

Declared interests

Dr Laura Sinclair: “· Dr Sinclair’s early research positions have been funded by the charities Animal Free Research UK and the Centre for Human Specific Research.

· Dr Sinclair leads the Phyto Ageing study team at the University of Exeter. The Phyto Ageing study is an early-stage, feasibility study investigating the effects of a plant-derived dietary supplement on ageing in the hands.

· Dr Sinclair is in the academic team of Prof Lorna Harries. Prof Harries’ academic team works alongside Prof Harries’ spin-out company, Senisca Ltd.

· Dr Sinclair is a Trustee of the British Society for Research on Ageing.”

Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, Gan & Lee, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Kailera, Mass Medicines, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi, Structure Therapeutics, UCB Pharma and Verdiva Bio; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche. He does not hold any stocks or shares in any medical companies.”

Prof Tara Spires-Jones: “I have no conflicts with this study but have received payments for consulting, grant reviews, scientific talks, or collaborative research over the past 10 years from AbbVie, Sanofi, Merck, Autifony, Scottish Brain Sciences, Jay Therapeutics, Cognition Therapeutics, Ono, Novo Nordisk, Eisai, Boehringer Ingelheim, and Bristol-Meyers Squibb and direct a company Spires-Jones Neuroscience, Ltd to act as a consultant. I am also Charity trustee for the British Neuroscience Association and serve as scientific advisor to several charities and non-profit institutions. My group receives grant funding for research from the UK Dementia Research Institute, Alzheimer’s Research UK, Alzheimer’s Society, Wellcome Trust, Medical Research Council, and the Foundations for the National Institutes of Health.”

For all other experts, no reply to our request for DOIs was received.