Lithocholic acid phenocopies anti-ageing effects of calorie restriction

作者：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, Sheng‐Cai Lin · 发表于：Nature · 年份：2024 · DOI：10.1038/s41586-024-08329-5 · 被引用次数：98 · 研究领域：Diet and metabolism studies、Genetics, Aging, and Longevity in Model Organisms、Antioxidants, Aging, Portulaca oleracea

; 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.