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Experimental Evolution of Aging: the genetic link between lifespan, nutrient sensing and fat metabolism

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Genes linked to living longer

Researchers on the project EvolAge have found two genes in fruit flies that affect how long they live. These genes and their variants affect not only ageing but also reproduction, and could offer future clues to help treat ageing humans.

Health

Two new genes were confirmed to affect lifespan in fruit flies, found researchers with EU project EvolAge. The finding could pave the way for vital future research to help humans live longer and more healthily. Both appear to be responsible for a variation in lifespan in response to the fruit fly postponing its reproduction, found Katja Hoedjes, who carried out the research at the University of Lausanne’s Keller Group, with support from the Marie Skłodowska-Curie programme. “Flies that were selected to reproduce later in life consistently evolved a longer lifespan,” Hoedjes says. “We also observed a small, but significant increase in lifespan in flies selected to develop on poor juvenile nutrition.” EvolAge identified 399 natural alleles – variants belonging to 154 genes that were strongly associated with differences in lifespan and which could play a role in regulating how long fruit flies live. “These promising genes are mostly novel ‘candidate genes’ for lifespan that have not been found in other studies before,” says Hoedjes, who was supervised by Laurent Keller, Professor of Ecology and Evolution at the University of Lausanne. The researchers then used additional genetic tests to confirm that two genes were indeed responsible for a variation in lifespan and, or, a change in reproduction. “Our methodology was a novel and powerful approach,” says Hoedjes.

New direction

The Keller Group specialises in research into why some insects live longer than others and how the evolution of social life is associated with a very long lifespan. In the past they had focused on ants, but thanks to the EU funding, the group was able to look for the first time at the Drosophila melanogaster fruit fly, an outstanding model organism for genetic studies due to its short generation times and easy rearing, which helped the experimental evolution. Hoedjes studied a set of experimentally evolved lines of Drosophila melanogaster that had been subjected to two selection procedures. The flies had been selected to reproduce later in life, to see the effect of reproduction on ageing, and also reared on different diets (a normal one and one with a reduced amount of nutrients in the juvenile stage). As well as identifying the two promising genes and the anti-ageing effects of their specific alleles, the EU project also tested the hypothesis that individual fruit flies with a higher fat content would have longer lifespans. “We did not observe consistent differences in fat content between populations with different lifespans and, also, it does not seem that genes controlling fat metabolism have an effect on lifespan in our populations,” says Hoedjes. The researchers believe their fundamental research into simple model species like the fruit fly is crucial for discovering the genetic pathways that are important in ageing. “In most modern societies humans tend to live longer and face a range of ageing-related diseases,” says Hoedjes. “A better understanding of the genetic processes that underlie variation in aging may provide important, novel insights into how to prevent these problems.”

Keywords

EvolAge, genes, fruit flies, ageing, alleles, Drosophila melanogaster

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