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Biochem 2024;175(5):525–537  \n[https://doi.org/10.1093/jb/mvae015](https://doi.org/10.1093/jb/mvae015)  \nJB Review  \nTherapeutic strategies targeting cellular senescence for cancer and other diseases  \nReceived 17 November 2023; accepted 30 January 2024; published online 15 February 2024  \nXuebing Wang1 , Takeshi Fukumoto2 ,† and Ken-ichi Noma1 ,3 , ∗  \n1Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-0815, Japan ; 2Division of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan; and  \n3Institute of Molecular Biology, University of Oregon, 1370 Franklin Blvd, Eugene, OR 97403, USA  \n∗ Ken-ichi Noma, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-Ku, Sapporo 060-0815, Japan. Tel.:+81-11-706-5071, Fax: +81-11-706-7540, email: [noma@igm.hokudai.ac.jp](noma@igm.hokudai.ac.jp)  \n†Takeshi Fukumoto, Division of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, 7-5-1  \nKusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. Tel.: +81-78-382-6134, Fax: +81-78-382-6149, email: [fuku@med.kobe-u.ac.jp](fuku@med.kobe-u.ac.jp)  \nCellular senescence occurs in response to endogenous or exogenous stresses and is characterized by stable cell cycle arrest, alterations in nuclear morphology and secretion of proinflammatory factors, referred to as the senescence-associated secretory phenotype (SASP). An increase of senescent cells is associated with the development of several types of cancer and aging-related diseases. Therefore, senolytic agents that selectively remove senescent cells may offer opportunities for developing new therapeutic strategies against such cancers and aging-related diseases. This review outlines senescence inducers and the general characteristics of senescent cells. We also discuss the involvement of senescent cells in certain cancers and diseases. Finally, we describe a series ofsenolytic agents and their utilization in therapeutic strategies.  \nGraphical Abstract  \nKeywords: aging, cancer, cellular senescence, premature aging (progeria) syndromes, senescence-and  \naging-related diseases, senolytic agents.  \nInducers of Cellular Senescence  \nCellular senescence is a state of stable cell cycle arrest triggered by various stimuli (1, 2) . In this review, we first outline how telomere shortening, oncogene activation and anticancer treatments elicit replicative senescence (RS), oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), respectively.  \nReplicative senescence  \nReplicative senescence (RS) is the first type of cellular senescence discovered, and it was first described in 1961, by scientists at the Wistar Institute (3) . In this pioneering study, primary human fibroblasts were observed to reach a state of irreversible cell cycle arrest after exhaustion of their finite replication capacity. Subsequently, it was shown that RS is caused by telomere shortening (3, 4) . Mechanistically, short telomeres induce a DNA damage response (DDR); consequently, the p53 tumor suppressor is phosphorylated and stabilized, leading to p21-dependent cell cycle arrest (2, 5, 6) .  \nOncogene-induced senescence  \nThe activation of oncogenes can trigger cellular senescence, known as oncogene-induced senescence (OIS)  \nCancer  \nProgeria  \nSenescence induction  \nChemotherapy  \nInflammation  \nInflammation  \nChemoresistance Cancer recurrence  \nPremature aging features  \nSASP factors  \nAccumulation ofsenescent cells  \nParacrine  \nSenolytic  \nElimination of  \nNeighboring cell Malignant cell Senescent cell senescent cells  \n© The Author(s) 2024 . Published by Oxford University Press on behalf of the Japanese Biochemical Society.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ([https://creativecommons.org/](https://creativecommons.org/)[ ](https://creativecommons.org/)[l","cbCaiokvOtzvPo4N","https://ap.wps.com/l/cbCaiokvOtzvPo4N","pdf",707833,13,"English","# Inducers of Cellular Senescence\n## Replicative senescence\n## Oncogene-induced senescence\n## Therapy-induced senescence\n# Features of Senescent Cells\n## Cell-cycle arrest","[{\"question\":\"What is cellular senescence and what defines it?\",\"answer\":\"Cellular senescence is stable cell-cycle arrest triggered by cellular stresses. It is characterized by nuclear morphology changes and secretion of proinflammatory factors via the senescence-associated secretory phenotype (SASP).\"},{\"question\":\"Why are senolytic strategies considered for cancer and aging-related diseases?\",\"answer\":\"An increase in senescent cells is associated with several cancers and aging-related diseases. Selectively removing senescent cells may enable new therapeutic strategies against these conditions.\"},{\"question\":\"How do anticancer therapies induce therapy-induced senescence (TIS)?\",\"answer\":\"Chemotherapy and radiotherapy can cause DNA damage that activates DNA damage response pathways (ATM/CHK2 and ATR/CHK1), leading to p53 activation. The severity of DNA damage influences whether cells become senescent or apoptotic after treatment.\"}]","Therapeutic strategies targeting cellular senescence for cancer and other diseases | PDF",1789996360,33]