Cellular senescence: a key therapeutic target in aging and diseases

Lei Zhang, Louise E. Pitcher, Matthew J. Yousefzadeh, Laura J. Niedernhofer, Paul D. Robbins, Yi Zhu

Research output: Contribution to journalReview articlepeer-review

134 Scopus citations


Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop a characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary senescence and disrupts tissue homeostasis, resulting in loss of tissue repair and regeneration. The use of transgenic mouse models in which SnCs can be genetically ablated has established a key role for SnCs in driving aging and age-related disease. Importantly, senotherapeutics have been developed to pharmacologically eliminate SnCs, termed senolytics, or suppress the SASP and other markers of senescence, termed senomorphics. Based on extensive preclinical studies as well as small clinical trials demonstrating the benefits of senotherapeutics, multiple clinical trials are under way. This Review discusses the role of SnCs in aging and age-related diseases, strategies to target SnCs, approaches to discover and develop senotherapeutics, and preclinical and clinical advances of senolytics.

Original languageEnglish (US)
Article numbere158450
JournalJournal of Clinical Investigation
Issue number15
StatePublished - Aug 1 2022

Bibliographical note

Funding Information:
This work was supported by NIH grants U19-AG056278, P01-AG043376, R01-AG063543, P01-AG062413, and U54-AG076041; by Aligning Science Across Parkinson’s grant ASAP-000592 from the Michael J. Fox Foundation; and by the Glenn Foundation for Medical Research. LEP is supported by National Institute on Aging Training Grant T32-AG029796. We thank Esben Iversen and Mas-ayoshi Suda for helpful discussions.

Publisher Copyright:
© 2022 American Society for Clinical Investigation. All rights reserved.


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