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Researchers from Queen Mary University of London finds that directly activating a key cellular energy sensor extended lifespan in yeast, worms and flies, offering new clues about the biology of ageing.

Scientists have taken an important step towards understanding how the biological processes of ageing might one day be targeted to help people live healthier for longer.

Research involving Queen Mary University of London has found that directly activating AMP-activated protein kinase (AMPK) – an ancient enzyme that helps cells respond when energy levels are low – extended lifespan in three very different organisms: fruit flies, nematode worms and fission yeast.

The study, published in Aging Cell, provides new evidence that AMPK could be a potential target for future research into longevity and healthy ageing.

AMPK acts as a cellular fuel sensor. When energy is running low, it helps cells adapt by increasing processes involved in energy production and recycling, while reducing growth. Scientists have suspected for years that this pathway is connected to ageing, but directly testing its role with a drug has been challenging.

In this study, researchers used a compound called 991, which binds directly to AMPK and switches it on. Unlike drugs such as metformin, which can activate AMPK indirectly while affecting other biological pathways, 991 allowed the researchers to test more directly whether activating AMPK itself could influence lifespan.

The results showed that 991 extended lifespan in fruit flies, worms and fission yeast. Crucially, when researchers used worms and yeast without functional AMPK, the lifespan-extending effect was no longer seen. This provides evidence that the effect was specifically dependent on AMPK activation.

The researchers also found that more was not necessarily better. Higher doses of 991 shortened lifespan in some experiments, highlighting the importance of getting the level of AMPK activation and nutritional conditions right.

The team also investigated what happened when 991 was administered to mice. After three weeks of treatment, analysis of liver proteins showed changes consistent with AMPK activation, including increased processes associated with ATP production and mitochondrial biogenesis, alongside suppression of the growth-promoting mTOR pathway.

However, the researchers stress that these mouse experiments did not demonstrate lifespan extension. The changes observed are molecular signatures associated with AMPK activation and longevity-related processes, and longer-term studies are needed to determine whether direct AMPK activation can extend mammalian lifespan and improve healthspan.

Dr Charalampos Rallis, Reader in Genetics, Genomics and Fundamental Cell Biology at Queen Mary University of London and co-author of the study, said:

"When a cell runs low on energy, AMPK is what kicks in to help it cope. We have known for years that this switch is connected to ageing. What we did not have was a drug clean enough to test the idea properly and with 991 we finally did. I would not want anyone to reach for a supplement on the back of this. Too much of the drug shortened life in our experiments. This is a switch that must be set correctly, not jammed on."

The research brings together 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.

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

You can read the full research via the following link.