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Review
. 2023 Oct;22(10):e13948.
doi: 10.1111/acel.13948. Epub 2023 Aug 7.

Strategies for senolytic drug discovery

Helen Power  1   2   3 , Peter Valtchev  1   2 , Fariba Dehghani  1   2 , Aaron Schindeler  1   2   3
Affiliations
Review

Strategies for senolytic drug discovery

Helen Power et al. Aging Cell. 2023 Oct.

Abstract

Senolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age-related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics-kinase inhibitors, Bcl-2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti-cancer drugs, cardiac steroids, PPAR-alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high-quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single-cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre-clinical models and human trials.

Keywords: cellular senescence; drug discovery; senescence; senolytics.

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Conflict of interest statement

The authors have no competing interests to declare.

Figures

FIGURE 1
FIGURE 1
Current categories of senolytics.
FIGURE 2
FIGURE 2
Methods for inducing a senescent phenotype.
FIGURE 3
FIGURE 3
Methods for confirming induction of a senescent phenotype.
FIGURE 4
FIGURE 4
The basic workflow for detecting novel senolytic compounds.
See this image and copyright information in PMC

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