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High-content screening identifies ganoderic acid A as a senotherapeutic to prevent cellular senescence and extend healthspan in preclinical models

文献类型： 外文期刊

作者： Chen, Li 1 ; Wu, Bangfu 1 ; Mo, Li 1 ; Chen, Huimin 1 ; Yin, Xingzhu 1 ; Zhao, Ying 1 ; Cui, Zhaoyu 1 ; Cui, Feipeng 1 ; Chen, Liangkai 1 ; Deng, Qianchun 3 ; Gao, Chao 5 ; Yao, Ping 1 ; Li, Yanyan 6 ; Tang, Yuhan 1 ;

作者机构： 1.Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Nutr & Food Hyg, Hubei Key Lab Food Nutr & Safety,Minist Educ Key L, Wuhan, Peoples R China

2.Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth,Minist Environm Protect, Key Lab Environm & Hlth Wuhan,MOE Key Lab of Envir, Wuhan, Peoples R China

3.Minist Agr Oil Crops & Lipids Proc Technol, Oil Crops Res Inst Chinese Acad Agr Sci, Hubei Key Lab Lipid Chem & Nutr, Natl & Local Joint Engn Lab, Wuhan, Hubei, Peoples R China

4.Minist Agr Oil Crops & Lipids Proc Technol, Key Lab Oilseeds Proc, Natl & Local Joint Engn Lab, Wuhan, Hubei, Peoples R China

5.Chinese Ctr Dis Control & Prevent, Natl Inst Nutr & Hlth, Beijing, Peoples R China

6.Shenzhen Ctr Chron Dis Control, Shenzhen, Peoples R China

期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）

ISSN：

年卷期： 2025 年 16 卷 1 期

页码：

收录情况： SCI

摘要： Accumulated senescent cells during the aging process are a key driver of functional decline and age-related disorders. Here, we identify ganoderic acid A (GAA) as a potent anti-senescent compound with low toxicity and favorable drug properties through high-content screening. GAA, a major natural component of Ganoderma lucidum, possesses broad-spectrum geroprotective activity across various species. In C. elegans, GAA treatment extends lifespan and healthspan as effectively as rapamycin. Administration of GAA also mitigates the accumulation of senescent cells and physiological decline in multiple organs of irradiation-stimulated premature aging mice, natural aged mice, and western diet-induced obese mice. Notably, GAA displays a capability to enhance physical function and adapts to conditional changes in metabolic demand as mice aged. Mechanistically, GAA directly binds to TCOF1 to maintain ribosome homeostasis and thereby alleviate cellular senescence. These findings suggest a feasible senotherapeutic strategy for protecting against cellular senescence and age-related pathologies.

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