Scientists at Nanyang Technological University experimented with a type of roundworm that shares similarities with humans and fed them a high-glucose diet to switch on their cells' stress response, called the unfolded protein response. Doing so extended the roundworms' lifespan compared with worms fed a normal diet (Nature Communications, October 19, 2022).

Roundworms (Caenorhabditis elegans) were fed a high-glucose diet at two different life stages: young (i.e., at the start of their adulthood) (day 1), and at a post-reproductive age (day 5), when the worms were aged and no longer fertile. A control group of worms was fed a normal diet throughout.

The aged worms given a high-glucose diet lived almost twice as long as young worms given the same diet (24 days versus 13 days). Worms on a normal diet lived for 20 days. The aged worms on the high-glucose diet were also more agile and had more energy storage cells than worms given a normal diet.

When looking at the three stress sensors responsible for a cellular pathway in the unfolded protein response, the scientists found one of the stress sensors, IRE1, was significantly more active in young worms compared with aged worms. When the gene coding was switched off, young worms fed a high-glucose diet from day 1 lived for 25 days -- twice as long as when the IRE1 gene was intact.

The findings suggest the increased activity of stress sensor IRE1 seen in young worms fed a high-glucose diet from day 1 was responsible for shortening their lifespan.

A drug that reduces the activity of IRE1 while increasing the activity of the other two stress sensors could potentially be developed to decelerate cellular aging and extend lifespans in humans, according to the researchers.

More studies are needed to dissect the mechanism behind the lifespan extension induced by a high-glucose diet, and how this can apply to humans because a high-glucose diet does not induce the same longevity effect in people.

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