Killing wisely: Precision senolytics in the age of frailty Review
| Authors: | Barthet, V. J. A.; Lowe, S. W. |
| Review Title: | Killing wisely: Precision senolytics in the age of frailty |
| Abstract: | Cellular senescence plays a dual role in tissue biology by promoting tumor suppression and wound healing when transient but driving inflammation, fibrosis, and agerelated disease when persistent. The growing recognition that senescent cell clearance can reverse these pathologies has catalyzed efforts to develop therapeutics that preferentially kill senescent cells (also known as “senolytics”). However, clinical translation from bench to bedside remains challenging due to senescent state heterogeneity, limited biomarkers, off-target toxicities, and the frailty of aged patients. Small molecule senolytics, although promising, often lack defined mechanisms of action and pose safety concerns that may constrain their use in older adults. Emerging precision approaches, including those that exploit surface markers and leverage engineered immune therapies, offer a rational and potentially more selective path forward. Here we highlight recent advances in senescence profiling and targeted clearance strategies, emphasizing the need for therapies designed with both biological complexity and the needs of aging populations in mind. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | aged; drug safety; biological marker; animal; animals; drug effect; age; immunotherapy; aging; drug therapy; cell aging; personalized medicine; cell surface; synthetic biology; procedures; cellular senescence; frailty; humans; human; article; precision medicine; senotherapeutics; senotherapeutic agent |
| Journal Title: | Genes and Development |
| Volume: | 39 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2025-09-01 |
| Start Page: | 910 |
| End Page: | 913 |
| Language: | English |
| DOI: | 10.1101/gad.353134.125 |
| PUBMED: | 40664503 |
| PROVIDER: | scopus |
| PMCID: | PMC12315863 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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