Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan  

作　　者：Jia-Yu Liu Yao Wang Yue Guo Run-Qi Zheng Yun-Ying Wang Yan-Yan Shen Yan-Hong Liu Ai-Ping Cao Rui-Bo Wang Bo-Yang Xie Shuai Jiang Qiu-Ying Han Jing Chen Fang-Ting Dong Kun He Na Wang Xin Pan Tao Li Tao Zhou Ai-Ling Li Qing Xia Wei-Na Zhang 

机构地区：[1]Nanhu Laboratory,National Center of Biomedical Analysis,Beijing 100850,China

出　　处：《Science China(Life Sciences)》2025年第2期416-430,共15页中国科学(生命科学英文版)

基　　金：supported by the Research Foundation of Nanhu Laboratory(NSS2021CI05003);the National Natural Science Foundation of China(82273024 and 82022030)。

摘　　要：As the elderly population expands,the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial.As an FDA-approved drug for chronic cholestatic liver diseases,tauroursodeoxycholic acid(TUDCA),a natural bile acid,offers additional health benefits beyond liver protection.Here,we show that TUDCA extends the lifespan and healthspan of C.elegans.Importantly,oral supplementation of TUDCA improves fitness in old mice,including clinically relevant phenotypes,exercise capacity and cognitive function.Consistently,TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics.Mechanistically,we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity.This collaboration further alleviates aging-induced endoplasmic reticulum(ER)stress and facilitates protein homeostasis,thus offering resistance to aging.In summary,our findings uncover new molecular links between an endogenous metabolite and protein homeostasis,and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

关 键 词：tauroursodeoxycholic acid LIFESPAN healthspan protein homeostasis 

分 类 号：R73[医药卫生—肿瘤]