厦门大学林圣彩团队的一项最新研究发现石胆酸表现出热量限制的抗衰老作用。相关论文于2024年12月18日发表在《自然》杂志上。

据悉，热量限制（CR）是一种以促进健康和长寿为主题的饮食干预措施。热量限制在代谢物的产生和循环中引起不同的代谢变化。然而，目前尚不清楚是哪种代谢产物的改变，导致了热量限制的生理益处。

研究人员利用代谢组学分析在热量限制期间表现出丰度变化的代谢物，并进行随后的功能验证。研究人员发现石胆酸（LCA）是一种单独的代谢物，可以重现小鼠体内热量限制的作用。这些作用包括活化AMP激活的蛋白激酶（AMPK），增强细胞再生和恢复握力和跑步能力。

石胆酸还能激活AMPK，在秀丽隐杆线虫和黑腹果蝇中诱导延长寿命和延长健康的作用。因为秀丽隐杆线虫和黑腹果蝇不能合成石胆酸，这些结果表明，这些动物能够传递石胆酸的信号作用。在所有三种动物模型中，敲除AMPK可消除石胆酸诱导的表型。

总之，研究人员发现单独补充热量限制介导的上调代谢物石胆酸，可以以AMPK依赖的方式赋予后生动物抗衰老的益处。

附：英文原文

Title: Lithocholic acid phenocopies anti-ageing effects of calorie restriction

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, Yun, Chuyu, Chen, Junjie, Xue, Shengye, Zhang, Baoding, Zheng, Zhong-Zheng, Piao, Hai-Long, Jiang, Changtao, Guo, Hao, Shui, Guanghou, Deng, Xianming, Zhang, Chen-Song, Lin, Sheng-Cai

Issue&Volume: 2024-12-18

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.

DOI: 10.1038/s41586-024-08329-5

Source: https://www.nature.com/articles/s41586-024-08329-5