ACS-20/FATP4 mediates the anti-ageing effect of dietary restriction in C. elegans

Zi Wang, Lina Zou, Yiyan Zhang, Mengnan Zhu, Shuxian Zhang, Di Wu, Jianfeng Lan, Xiao Zang, Qi Wang, Hanxin Zhang, Zixing Wu, Huanhu Zhu and Di Chen ()
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Zi Wang: Nanjing University
Lina Zou: Nanjing University
Yiyan Zhang: Nanjing University
Mengnan Zhu: ShanghaiTech University
Shuxian Zhang: ShanghaiTech University
Di Wu: Zhengzhou University
Jianfeng Lan: Affiliated Hospital of Guilin Medical University
Xiao Zang: Nanjing University
Qi Wang: Nanjing University
Hanxin Zhang: Nanjing University
Zixing Wu: Nanjing University
Huanhu Zhu: ShanghaiTech University
Di Chen: Nanjing University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43613-4

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