蛋白质稳态
长寿
生物
调解人
秀丽隐杆线虫
转录因子
细胞生物学
抑制因子
遗传学
转录组
基因
基因表达
作者
Zi Wang,Lina Zou,Yiyan Zhang,Maoyan Zhu,Shuxian Zhang,Di Wu,Jianfeng Lan,Xiao Ping Zang,Qi Wang,Hanxin Zhang,Zixing Wu,Huanhu Zhu,Di Chen
标识
DOI:10.1038/s41467-023-43613-4
摘要
Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of PTR-8/Patched is responsible for the proteostasis and lifespan defects of acs-20. Furthermore, the conserved NHR-23 nuclear receptor serves as a transcriptional repressor of ptr-8 and a key regulator of dietary restriction-induced longevity. Mechanistically, a specific region in the ptr-8 promoter plays a key role in mediating the transcription regulation and lifespan extension under dietary restriction. Altogether, these findings identify a highly conserved lipid metabolism enzyme as a key mediator of dietary restriction-induced lifespan and healthspan extension and reveal the downstream transcriptional regulation mechanisms.
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