| RRC ID |
80750
|
| Author |
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.
|
| Title |
ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans.
|
| Journal |
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.
|
| Volume |
14(1)
|
| Pages |
7683
|
| Published |
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
|
| Resource |
| C.elegans |
tm3232 |
