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The fruit fly acetyltransferase chameau promotes starvation resilience at the expense of longevity

ABSTRACT: Proteins involved in cellular metabolism and molecular regulation can extend lifespan in various organisms in the laboratory. However, any improvement in aging would only provide an evolutionary benefit if the organisms were able to survive under non-ideal conditions. We have previously shown that Drosophila melanogaster carrying a loss of function allele of the acetyltransferase chameau (chm) has an increased healthy life span when fed ad libitum. Here, we show that loss of chm and a reduction of its activity result in a substantial reduction of weight and a decrease in starvation resistance. This phenotype is caused by a failure to properly regulate the genes and proteins required for energy storage and expenditure. The previously observed increase in survival time thus comes with the inability to prepare for and cope with nutrient stress. As the ability survive in environments with restricted food availability is likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism’s genome despite its apparent negative effect on lifespan.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE211042 | GEO | 2023/08/21

REPOSITORIES: GEO

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The Drosophila acetyltransferase chameau (chm) promotes starvation resilience at the expense of a shortened life span

Project description:Proteins involved in cellular metabolism and molecular regulation have been shown to extend lifespan in various laboratory organisms. However, for any improvement in aging to confer an evolutionary benefit, organisms must also be able to survive under non-ideal conditions. Earlier, we discovered that the loss of chm function and reduced activity resulted in several notable effects. Firstly, flies with a loss-of-function allele of chm exhibited an extended healthy lifespan when provided with an unrestricted food supply, indicating that chm plays a role in lifespan regulation. In this study, we demonstrate that these flies also experience a significant reduction in weight and decreased starvation resistance compared to flies with normal chm function. Furthermore, based on observations from transcriptomic, proteomic, and acetylome data, we hypothesize that chm is important for regulating metabolism in Drosophila, particularly in energy storage and utilization. Moreover, we demonstrate that reduced chm activity affects carbohydrate metabolism in flies at the basal level and during changes in nutrient status. In summary, this study suggests that chm is also required for starvation resilience by regulating carbohydrate metabolism, and the previously observed increase in survival time likely accompanies the inability to prepare for and cope with nutrient stress. Finally, as the ability to adapt and survive in a food-restricted environment was likely a stronger evolutionary driver than the ability to live a long life, chm is still present in the organism's genome despite its apparent deleterious effect on lifespan.

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