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 and Yuhan Tang ()
Additional contact information
Li Chen: Huazhong University of Science and Technology
Bangfu Wu: Huazhong University of Science and Technology
Li Mo: Huazhong University of Science and Technology
Huimin Chen: Huazhong University of Science and Technology
Xingzhu Yin: Huazhong University of Science and Technology
Ying Zhao: Huazhong University of Science and Technology
ZhaoYu Cui: Huazhong University of Science and Technology
Feipeng Cui: Huazhong University of Science and Technology
Liangkai Chen: Huazhong University of Science and Technology
Qianchun Deng: Ministry of Agriculture, Oil Crops and Lipids Process Technology National & Local Joint Engineering Laboratory
Chao Gao: Chinese Center for Disease Control and Prevention
Ping Yao: Huazhong University of Science and Technology
Yanyan Li: Shenzhen Center for Chronic Disease Control
Yuhan Tang: Huazhong University of Science and Technology

Nature Communications, 2025, vol. 16, issue 1, 1-23

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58188-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58188-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58188-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().