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Cell senescence

The prompt to discover senolytics

Nature Reviews Molecular Cell Biology volume 25, page 953 (2024)Cite this article

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“organ dysfunction and abundance of persistent senescent cells with a pro-apoptotic, pro-inflammatory phenotype do indeed appear to be causally linked”

Prompted by the Krishnamurthy et al. article, we asked whether the association between senescent cell accumulation and tissue or organ dysfunction was due to a causal effect of senescent cells. To test this, we initiated efforts to discover and develop senolytics in 2004 and subsequently, based on transgenic FAT-ATTAC mice (in which the ablation of fat cells can be induced; Pajvani et al., 2005), to design mice from which p16INK4A-expressing senescent cells can be selectively eliminated. In studies using senolytics and mouse models, organ dysfunction and the abundance of persistent senescent cells with a pro-apoptotic, pro-inflammatory phenotype do indeed appear to be causally linked. Hence, the prescient article by Krishnamurthy et al. prompted the development of senolytics that are currently in many early-phase clinical trials for disorders and diseases linked to cellular senescence.

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Original article

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Authors and Affiliations

  1. Center for Advanced Gerotherapeutics, Division of Endocrinology and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    James L. Kirkland

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  1. James L. Kirkland
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Correspondence to James L. Kirkland.

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Competing interests

The author has a financial interest related to this research: patents and pending patents covering senolytic drugs and their uses that are held by the author’s former institution, Mayo Clinic. This article was prepared in compliance with Mayo Clinic’s conflict of interest policies.

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Kirkland, J.L. The prompt to discover senolytics. Nat Rev Mol Cell Biol 25, 953 (2024). https://doi.org/10.1038/s41580-024-00795-z

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