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However, long\u2010term retention of senescent cells causes inflammation, aging of the tissue, and progression of deadly diseases such as obesity, diabetes, and atherosclerosis. Various attempts have been made to achieve selective elimination of senescent cells from the body, yet little has been explored in designing the mitochondria\u2010targeted senolytic agent. Many characteristics of senescence are associated with mitochondria. Here we have designed a library of alkyl\u2010monoquaternary ammonium\u2010triphenyl phosphine (TPP) and alkyl\u2010diquaternary ammonium\u2010TPP of varying alkyl chain lengths, which target the mitochondria; we also studied their senolytic properties. It was observed that the alkyl\u2010diquaternary ammonium\u2010TPP with the longest chain length induced apoptosis in senescent cells selectively via an increase of reactive oxygen species (ROS) and mitochondrial membrane disruption. This study demonstrates that mitochondria could be a potential target for designing new small molecules as senolytic agents for the treatment of a variety of dysfunctions associated with pathological aging.<\/jats:p>","DOI":"10.1002\/cbic.202100412","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T22:09:33Z","timestamp":1632780573000},"page":"3391-3397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mitochondrial Membrane Disrupting Molecules for Selective Killing of Senescent Cells"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2944-0109","authenticated-orcid":false,"given":"Batakrishna","family":"Jana","sequence":"first","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangpil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Byoung","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Konkuk University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Konkuk University School of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaekyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-0985","authenticated-orcid":false,"given":"Ja\u2010Hyoung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Chemistry Ulsan National Institute of Science and Technology (UNIST)  Ulsan 44919 South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"e_1_2_2_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3823"},{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03890"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10600"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02088-0"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.03.008"},{"key":"e_1_2_2_6_1","unstructured":"\u00a0"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-15-1021"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3928"},{"key":"e_1_2_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2012.11.009"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00042"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121837"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3365"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/ctm.ctm_22_18"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202002576"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202002576"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080063"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060919"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.06.045"},{"key":"e_1_2_2_18_1","doi-asserted-by":"crossref","unstructured":"Organelle-Specific Pharmaceutical Nanotechnology (Eds.: V. 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