Lithocholic acid phenocopies anti-ageing effects of calorie restriction

Qi Qu, Yan Chen, Yu Wang, Shating Long, Weiche Wang, Heng-Ye Yang, Mengqi Li, Xiao Tian, Xiaoyan Wei, Yan-Hui Liu, Shengrong Xu, Cixiong Zhang, Mingxia Zhu, Sin Man Lam, Jianfeng Wu, Chuyu Yun, Junjie Chen, Shengye Xue, Baoding Zhang, Zhong-Zheng Zheng, Hai-Long Piao, Changtao Jiang, Hao Guo, Guanghou Shui, Xianming Deng, Chen-Song Zhang () and Sheng-Cai Lin ()
Additional contact information
Qi Qu: Xiamen University
Yan Chen: Xiamen University
Yu Wang: Xiamen University
Shating Long: Xiamen University
Weiche Wang: Xiamen University
Heng-Ye Yang: Xiamen University
Mengqi Li: Xiamen University
Xiao Tian: Xiamen University
Xiaoyan Wei: Xiamen University
Yan-Hui Liu: Xiamen University
Shengrong Xu: Xiamen University
Cixiong Zhang: Xiamen University
Mingxia Zhu: Xiamen University
Sin Man Lam: LipidALL Technologies
Jianfeng Wu: Xiamen University
Chuyu Yun: Peking University Third Hospital
Junjie Chen: Xiamen University
Shengye Xue: Xiamen University
Baoding Zhang: Xiamen University
Zhong-Zheng Zheng: Xiamen University
Hai-Long Piao: Chinese Academy of Sciences
Changtao Jiang: Peking University
Hao Guo: Xiamen University
Guanghou Shui: Chinese Academy of Sciences
Xianming Deng: Xiamen University
Chen-Song Zhang: Xiamen University
Sheng-Cai Lin: Xiamen University

Nature, 2025, vol. 643, issue 8070, 192-200

Abstract: Abstract Calorie restriction (CR) is a dietary intervention used to promote health and longevity1,2. CR causes various metabolic changes in both the production and the circulation of metabolites1; however, it remains unclear which altered metabolites account for the physiological benefits of CR. Here we use metabolomics to analyse metabolites that exhibit changes in abundance during CR and perform subsequent functional validation. We show that lithocholic acid (LCA) is one of the metabolites that alone can recapitulate the effects of CR in mice. These effects include activation of AMP-activated protein kinase (AMPK), enhancement of muscle regeneration and rejuvenation of grip strength and running capacity. LCA also activates AMPK and induces life-extending and health-extending effects in Caenorhabditis elegans and Drosophila melanogaster. As C. elegans and D. melanogaster are not able to synthesize LCA, these results indicate that these animals are able to transmit the signalling effects of LCA once administered. Knockout of AMPK abrogates LCA-induced phenotypes in all the three animal models. Together, we identify that administration of the CR-mediated upregulated metabolite LCA alone can confer anti-ageing benefits to metazoans in an AMPK-dependent manner.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-024-08329-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:643:y:2025:i:8070:d:10.1038_s41586-024-08329-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-024-08329-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().