RRC ID 80750
著者 Wang Z, Zou L, Zhang Y, Zhu M, Zhang S, Wu D, Lan J, Zang X, Wang Q, Zhang H, Wu Z, Zhu H, Chen D.
タイトル ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans.
ジャーナル Nat Commun
Abstract 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.
巻・号 14(1)
ページ 7683
公開日 2023-11-24
DOI 10.1038/s41467-023-43613-4
PII 10.1038/s41467-023-43613-4
PMID 38001113
PMC PMC10673863
MeSH Aging / genetics Animals Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / metabolism Caloric Restriction Carrier Proteins / metabolism Longevity / physiology Transcription Factors / metabolism
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