Effects of hunger on neuronal histone modifications slow aging in Drosophila

• 成果类型: Article
• 署名作者: Weaver, K. J.; Holt, R. A.; Henry, E.; Lyu, Y.; Pletcher, S. D.
• 署名单位: University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan; Rutgers University System; Rutgers University New Brunswick
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11700
• DOI: 10.1126/science.ade1662
• 发表日期: 2023-05-11
• 页码: 625-632
• 关键词: chain amino-acids; solid food-intake; life-span; variant h3.3; cellular-metabolism; dietary restriction; pox-neuro; longevity; chromatin; protein

摘要

Hunger is an ancient drive, yet the molecular nature of pressures of this sort and how they modulate physiology are unknown. We find that hunger modulates aging in Drosophila. Limitation of branched -chain amino acids (BCAAs) or activation of hunger-promoting neurons induced a hunger state that extended life span despite increased feeding. Alteration of the neuronal histone acetylome was associated with BCAA limitation, and preventing these alterations abrogated the effect of BCAA limitation to increase feeding and extend life span. Hunger acutely increased feeding through usage of the histone variant H3.3, whereas prolonged hunger seemed to decrease a hunger set point, resulting in beneficial consequences for aging. Demonstration of the sufficiency of hunger to extend life span reveals that motivational states alone can be deterministic drivers of aging.