Mizutani, S., Furuya, K., Mure, A., Takahashi, Y., Mori, A., Sakurai, N., Suito, T., Nagao, K., Umeda, M., Watanabe, K., Hattori, Y., Uemura, T. (2025). Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males.  EMBO Rep. 26(15): 3856--3888.

FBrf0263118

Research paper

The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with Drosophila melanogaster as a model, we fed larvae on diets consisting of a variety of yeast mutants and explored the resulting histories that impacted adult lifespan. A larval diet comprised of yeast nat3 KO shortened the lifespan of male adults; and remarkably, this diet diminished the function of histone acetyltransferase Gcn5 in larvae. Concordantly, perturbation of Gcn5-mediated gene regulation in the larval whole body or neurons significantly contributed to the earlier death of adults. The nat3 KO diet is much more abundant in long-chain fatty acids and branched-chain amino acids (BCAAs) than the control yeast diet. Supplementing the control diet with a combination of oleic acid, valine, and acetic acid recapitulated the effects of the nat3 KO diet on the larval transcriptome and the lifespan of males. Our findings strongly suggest a causal link between a fatty acids- and BCAA-rich diet in developmental stages and lifespan reduction via the adverse effect on the Gcn5 function.

PMC12332192 (PMC) (EuropePMC)