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Senolytic Drugs: Implications for Clinical Practice

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Abstract

Studying the mechanisms of aging is one of the most important goals of modern science. A significant amount of data on the processes associated with a decrease in the functional ability to regenerate, cell proliferation and resistance to adverse factors with age has been accumulated due to fundamental research. The aim of the review was to study the mechanism of drugs with the senolytic activity, to determine the main targets of their effect at the cellular level, and also to evaluate the prospects for their clinical use. The relevance of this topic is confirmed by the increasing number of clinical trials of senolytics, many of which have ambiguous results and require further analysis and elimination of revealed difficulties and shortcomings. We reviewed the literature on Pubmed and Scopus platforms over the past 10 years in order to find information about the mechanisms of senotherapy and the possibility of using senolytics in clinical medicine. The focus was on those senolytic drugs that were used in clinical studies.

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Funding was provided under the Priority 2030 program.

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Authors and Affiliations

  1. Russian Gerontology Research and Clinical Center, Pirogov National Research Medical University, Institute for Aging Research, Moscow, Russia

    A. K. Ilyushchenko, L. V. Matchekhina, O. N. Tkacheva, A. V. Balashova, A. A. Melnitskaia, A. V. Churov & I. D. Strazhesko

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  1. A. K. Ilyushchenko
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  2. L. V. Matchekhina
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Correspondence to A. K. Ilyushchenko.

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Abbreviations: SASP, senescence-associated secretory phenotype; TNF-α, tumor necrosis factor α; AMPK, AMP-activated protein kinase; EGFR, epidermal growth factor receptor; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; SASP, senescence-associated secretory phenotype; TGF-β, transforming growth factor β; VEGF, vascular endothelial growth factor; p21CIP1, cyclin-dependent kinase inhibitor 1; SAHF, senescence-associated heterochromatin foci; P53, transcription factor, tumor suppressor; FOXO, transcription factor of the Forkhead subclass O family; PI3K, phosphoinositide 3-kinase; EGF, epidermal growth factor; JAK, cytoplasmic proteins of the Janus kinase family; STAT, family of signaling proteins that regulate transcription; NF-κB, universal transcription factor that controls expression of immune response, apoptosis and cell cycle genes; Bcl2 and BclX, antiapoptotic proteins; AKT, protein kinase, also known as protein kinase B (PKB); ATM, ataxia telangiectasia mutated, signal DDR kinases; ATR, ataxia telangiectasia and Rad3 related, signal DDR kinase; CFS, cytosolic chromatin fragments; DDR, DNA damage response; HSF-1, heat shock transcription factor 1; IL-6, IL-1α, proinflammatory interleukins; INK4/ARF, gene locus, encodes key effectors of cell growth arrest (p15INK4B, p16, and ARF); MCP1 (=CCL2), monocyte chemoattractant protein 1; MDC1, mediator of DNA damage checkpoint 1; NRF2, nuclear factor-E2-related factor 2; p16INK4a, tumor suppressor; Rb, retinoblastoma protein, tumor suppressor protein; SC, senescent cell.

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Ilyushchenko, A.K., Matchekhina, L.V., Tkacheva, O.N. et al. Senolytic Drugs: Implications for Clinical Practice. Adv Gerontol 13, 62–69 (2023). https://doi.org/10.1134/S2079057024600186

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