Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten adult lifespan

ABSTRACT: 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 adult lifespan; 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 adult lifespan. 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.

ORGANISM(S): Saccharomyces cerevisiae (brewer's yeast) Drosophila melanogaster (fruit fly)

SUBMITTER:  

PROVIDER: S-BSST1869 | biostudies-other |

SECONDARY ACCESSION(S): PRJDB17027

REPOSITORIES: biostudies-other