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

Proteins involved in cellular metabolism and molecular regulation can extend lifespan of 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 lifespan when fed ad libitum . Here, we show that loss of chm and reduction in its activity results in a substantial reduction in weight and a decrease in starvation resistance . This phenotype is caused by 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 to 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. image The fruit fly acetyltransferase chameau (chm) plays a role in controlling stress resilience. Our study provides an explanation for the chameau‐mediated shortening of the lifespan. Chm mutant flies are in a state of constant caloric restriction, which is beneficial for extending their lifespan but detrimental if the animals face nutritional challenges. The acetyltransferase chm plays a significant role in the physiology of fruit flies. Mutant chm flies exhibit misregulation of genes and proteins involved in metabolic processes, including alterations in protein acetylation. Fruit flies lacking chm have an extended lifespan but are more susceptible to starvation. The primary importance of chm in addressing phenotypic defects is observed within the fat body, a specific tissue in fruit flies. Tissue‐specific expression of chm rescues the changes in physiology and the ability to respond to starvation.