Author:
Qu Qi,Chen Yan,Wang Yu,Long Shating,Wang Weiche,Yang Heng-Ye,Li Mengqi,Tian Xiao,Wei Xiaoyan,Liu Yan-Hui,Xu Shengrong,Zhang Cixiong,Zhu Mingxia,Lam Sin Man,Wu Jianfeng,Zhang Baoding,Zheng Zhong-Zheng,Piao Hai-Long,Shui Guanghou,Deng Xianming,Zhang Chen-Song,Lin Sheng-Cai
Abstract
Calorie restriction (CR) is a dietary intervention to promote health and longevity. CR causes various metabolic changes in both the production and circulation of metabolites; however, it remains unclear which of the changed metabolite(s) can account for the physiological benefits of CR. Through metabolomic analysis of metabolites undergoing abundance changes during CR and subsequent functional validation, we found that lithocholic acid (LCA) is the only metabolite that alone can recapitulate the effects of CR, including activation of AMPK and the rejuvenating effects of muscle regeneration, grip strength and running capacity in mice. Interestingly, LCA also activates AMPK and exerts life- and health-extending effects inCaenorhabditis elegansandDrosophila melanogaster, indicating that these animal models are able to transmit the signalling of LCA once administered. Knockout of AMPK abrogates LCA-induced phenotypes, in nematodes and flies, as well as in mice. Together, we have identified that administration of the CR-upregulated metabolite LCA alone can confer anti-ageing benefits to metazoans, in an AMPK-dependent manner.
Publisher
Cold Spring Harbor Laboratory