Scientists find ‘switch’ to potentially unlock longer lifespans

By Lauren Wilkin

Scientists have taken an important step toward understanding how we age — and how to extend our lifespan.

The research — involving Queen Mary University of London — found that an ancient enzyme called AMPK helps cells when energy levels are low.

During the study, this enzyme extended the lifespan of 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 aging in humans.

The researchers say that AMPK acts as a fuel sensor for cells. When energy is running low, it helps cells adapt by increasing energy production and recycling, while reducing growth.

Scientists have suspected for years that this pathway is connected to aging, but directly testing its role with a drug has been challenging.

In this study, researchers used a compound called 991, which binds to AMPK and "switches it on."

The compound 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.

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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 — meaning getting the level of AMPK activation right is essential.

The team also investigated what happened when 991 was administered to mice. While after three weeks of treatment, researchers found signs of AMPK activation, the mouse experiments did not demonstrate lifespan extension.

However, the changes observed in the mice were longevity-related processes, so researchers say that longer-term studies will be needed to determine whether direct AMPK activation can extend mammalian lifespan and improve healthspan.

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 aging. What we did not have was a drug clean enough to test the idea properly and with 991 we finally did."

But Rallis warns: "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 group brough 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 Universite Claude Bernard Lyon 1.

The group says 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.