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

Li Chen, Bangfu Wu, Li Mo, Huimin Chen, Xingzhu Yin, Ying Zhao, ZhaoYu Cui, Feipeng Cui, Liangkai Chen, Qianchun Deng, Chao Gao, Ping Yao, Yanyan Li, Yuhan Tang

Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Laboratory of Environment and Health and MOE Key Lab of Environment and Health, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. · pubmed

Paper

Abstract

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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Research summary

Ganoderic acid A (GAA) is identified as a senotherapeutic compound that prevents cellular senescence and extends healthspan in preclinical models. This paper is relevant as it addresses the root causes of aging by targeting cellular senescence, which is a significant contributor to age-related decline and diseases.

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