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<p>The nutritional environment in early life, referred to as the nutrition history, exerts far-reaching health effects beyond the developmental stage. Here, with <i>Drosophila melanogaster</i> 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 <i>nat3</i> KO shortened the lifespan of male adults; and remarkably, this diet diminished the function of histone acetyltransferase Gcn5 in larvae. Concordantly, perturbation of <i>Gcn5</i>-mediated gene regulation in the larval whole body or neurons significantly contributed to the earlier death of adults. The <i>nat3</i> 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 <i>nat3</i> 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.</p>

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Growth phase diets diminish histone acetyltransferase Gcn5 function and shorten lifespan of Drosophila males

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月10日

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  • Shoko Mizutani,
  • Kanji Furuya,
  • Ayumi Mure,
  • Yuuki Takahashi,
  • Akihiro Mori,
  • Nozomu Sakurai,
  • Takuto Suito,
  • Kohjiro Nagao,
  • Masato Umeda,
  • Kaori Watanabe,
  • Yukako Hattori,
  • Tadashi Uemura

摘要

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.