Scientists have made an important advance in understanding how the biological mechanisms of ageing could potentially be targeted to support healthier and longer lives.

A study involving researchers from Queen Mary University of London found that directly activating AMP-activated protein kinase (AMPK), an enzyme that helps cells respond to low energy levels, extended lifespan in three different organisms: fruit flies, nematode worms and fission yeast.

Published in Aging Cell, the research provides new evidence that AMPK may be a potential target for future studies focused on longevity and healthy ageing.

AMPK functions as a cellular energy sensor. When energy levels fall, it helps cells adapt by promoting energy production and recycling while reducing growth-related processes. Although scientists have long suspected that AMPK plays a role in ageing, directly testing this pathway with a drug has been challenging.

For the study, researchers used a compound known as 991, which binds directly to AMPK and activates it. Unlike drugs such as metformin, which can influence AMPK indirectly while affecting other pathways, 991 allowed researchers to examine more specifically whether AMPK activation itself could affect lifespan.

The researchers found that treatment with 991 increased lifespan in fruit flies, worms and fission yeast. Importantly, the effect disappeared in worms and yeast that lacked functional AMPK, indicating that the lifespan extension depended on AMPK activation.

The findings also showed that greater activation was not necessarily beneficial. At higher doses, 991 shortened lifespan in some experiments, suggesting that the level of AMPK activation and nutritional conditions may be important.

Researchers also examined the effects of 991 in mice. After three weeks of treatment, liver protein analysis revealed molecular changes consistent with AMPK activation, including increased processes linked to ATP production and mitochondrial biogenesis, along with reduced activity of the growth-promoting mTOR pathway. However, these experiments did not demonstrate lifespan extension in mice, and longer-term studies are needed to determine whether direct AMPK activation can improve healthspan or extend lifespan in mammals.

Dr Charalampos Rallis, Reader in Genetics, Genomics and Fundamental Cell Biology at Queen Mary University of London and a co-author of the study, emphasized that the findings should not be interpreted as a reason to use supplements or similar products. The study showed that excessive activation could have harmful effects, highlighting the importance of carefully regulating the pathway.

The research involved scientists from Queen Mary University of London, the MRC Laboratory of Medical Sciences, Imperial College London, the University of Cologne, the Francis Crick Institute and Université Claude Bernard Lyon 1.

Overall, the findings provide a foundation for further research into whether directly targeting AMPK could eventually contribute to interventions designed not only to extend lifespan, but also to help people remain healthier for longer.

Source: https://www.qmul.ac.uk/news/latest-news/2026/science-and-engineering/se/scientists-are-a-step-closer-to-understanding-and-extending-lifespan.html