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Senolytics: Targeting Senescent Cells for Age-Associated Diseases

  • Molecular Biology of Cell Death and Aging (N Razdan and N Muhammad, Section Editors)
  • Published:
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Abstract

Purpose of Review

Evidence suggests that senescent cells drive aging and age-related diseases, with interventions that clear them improving various conditions in preclinical models. Efforts to discover senolytics, drugs that can specifically kill senescent cells, are ongoing, guided by studies into their biology and several in vivo models. This review describes recently discovered senolytics and the pathways they target.

Recent Findings

Drugs targeting the BCL-2 family proteins, p53 activators, HSP90 inhibitors, cardiac glycosides, and fibrates along with several flavonoids are senolytic in vitro and in vivo. Methods for specifically delivering death to senescent cells to decrease non-specific off-target effects take advantage of their characteristic elevated level of p16 and increased β-galactosidase activity.

Summary

Effects of senolytics on age-related diseases in pre-clinical models have been so striking that several proof-of-concept and safety phase I human trials have begun. The search continues for additional senolytics that can target more types of senescent cells with the least side effects.

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Acknowledgments

This work was supported by Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty (M.X.), and NIH grants R21AG063528 (G.A.K. and M.X.).

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Authors and Affiliations

  1. UConn Center on Aging, UConn Health, 263 Farmington Avenue, EM013, Farmington, CT, 06030-1835, USA

    Iman M. A. Al-Naggar, George A. Kuchel & Ming Xu

  2. Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, USA

    Ming Xu

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  1. Iman M. A. Al-Naggar
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  2. George A. Kuchel
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  3. Ming Xu
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Correspondence to Iman M. A. Al-Naggar.

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Conflict of Interests

Dr. Xu has financial interest related to senolytics. Patents on senolytic drugs (including PCT/US2016/041646, filed at the US Patent Office) are held by Mayo Clinic. Dr. Kuchel has nothing to disclose. Dr. Al-Naggar has nothing to disclose.

Human and Animal Rights and Informed Consent

All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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This article is part of the Topical Collection on Molecular Biology of Cell Death and Aging

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Al-Naggar, I.M.A., Kuchel, G.A. & Xu, M. Senolytics: Targeting Senescent Cells for Age-Associated Diseases. Curr Mol Bio Rep 6, 161–172 (2020). https://doi.org/10.1007/s40610-020-00140-1

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