The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
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 age-related 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.
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Senolytic therapy has progressed from a conceptual framework to a sophisticated field at the intersection of geroscience, immunotherapy, and chemical biology.
“Senolytic therapy has progressed from a conceptual framework to a sophisticated field at the intersection of geroscience, immunotherapy, and chemical biology139,140.”
From Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming (2026) · cites this paper as [140]
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Cites
Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders
Baker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., Kirkland, J. L., & van Deursen, J. M. (2011) · Nature · doi:10.1038/nature10600 · Cited by 3,670 · cited 1×
“Indeed, in-depth molecular characterization of various senescence contexts has un-covered distinct senescent subtypes with varying SASP composition, metabolic and immune interactions (Coppé et al. 2010; Baker et al. 2011; Zhu et al. 2015; Yosef et al. 2016; Childs et al. 2017; Xu et al. 2018).”
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs
Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., Palmer, A. K., Ikeno, Y., Hubbard, G. B., Lenburg, M., et al. (2015) · Aging Cell · doi:10.1111/acel.12344 · Cited by 2,584 · cited 1×
“Indeed, in-depth molecular characterization of various senescence contexts has un-covered distinct senescent subtypes with varying SASP composition, metabolic and immune interactions (Coppé et al. 2010; Baker et al. 2011; Zhu et al. 2015; Yosef et al. 2016; Childs et al. 2017; Xu et al. 2018).”
Senolytics improve physical function and increase lifespan in old age
Xu, M., Pirtskhalava, T., Farr, J. N., Weigand, B. M., Palmer, A. K., Weivoda, M. M., Inman, C. L., Ogrodnik, M. B., Hachfeld, C. M., Fraser, D. G., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0092-9 · Cited by 2,287
Senescent cells: an emerging target for diseases of ageing
Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.116 · Cited by 1,284
Senolytic CAR T cells reverse senescence-associated pathologies
Amor, C., Feucht, J., Leibold, J., Ho, Y.-J., Zhu, C., Alonso-Curbelo, D., Mansilla-Soto, J., Boyer, J. A., Li, X., Giavridis, T., et al. (2020) · Nature · doi:10.1038/s41586-020-2403-9 · Cited by 1,098
Self-citationDirected elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
Unmasking Transcriptional Heterogeneity in Senescent Cells
Hernandez-Segura, A., de Jong, T. V., Melov, S., Guryev, V., Campisi, J., & Demaria, M. (2017) · Current Biology · doi:10.1016/j.cub.2017.07.033 · Cited by 972 · cited 1×
“For example, senescent fibroblasts differ markedly in their transcriptional and secretory profiles depending on whether senescence was induced by irradiation, onco-gene activation, or injury (Hernandez-Segura et al. 2017).”
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NKG2D ligands mediate immunosurveillance of senescent cells
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- 10.1016/0014-4827(61)90192-6 · DOI · Paper page
- 10.1111/acel.13988 · DOI
- 10.3389/fcell.2021.645593 · DOI · Paper page
- 10.1038/nm0396-287 · DOI
- 10.1016/j.cell.2024.09.021 · DOI
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Emerging strategies in senotherapeutics: from broad-spectrum senolysis to precision reprogramming
Zhang, W., Song, S., Zhang, Y., Pan, Y., Hu, D., & Wang, Y. (2026) · npj Aging · doi:10.1038/s41514-026-00355-z · Cited by 6
Metadata
- Authors
- Barthet, V. J. A., & Lowe, S. W.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2025-07-15
- Volume
- 39
- Issue
- 15-16
- Pages
- 910-913
- ISSN
- 0890-9369
- 1549-5477
- PMC
- PMC12315863
- Cited by
- 13
- References
- 12
- Language
- en
- Funders
- Francois Wallace Monahan Postdoctoral Fellowship
- Cancer Research Institute Irvington Postdoctoral Fellowship (CRI5088)
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