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Senescence of different cardiac cell types can direct the pathophysiology of cardiovascular diseases (CVDs) such as atherosclerosis, myocardial infarction, and cardiac fibrosis. While age-related telomere shortening represents a major cause of replicative senescence, the senescent state can also be induced by oxidative stress, metabolic dysfunction, and epigenetic regulation, among other stressors. It is critical that we understand the molecular pathways that lead to cellular senescence and the consequences of cellular senescence in order to develop new therapeutic approaches to treat CVD. In this review, we discuss molecular mechanisms of cellular senescence, explore how cellular senescence of different cardiac cell types (including cardiomyocytes, cardiac endothelial cells, cardiac fibroblasts, vascular smooth muscle cells, and valve interstitial cells) can lead to CVD, and highlight potential therapeutic approaches that target molecular mechanisms of cellular senescence to prevent or treat CVD.<\/jats:p>","DOI":"10.1093\/cvr\/cvab161","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T18:03:24Z","timestamp":1620237804000},"page":"1173-1187","source":"Crossref","is-referenced-by-count":322,"title":["Senescence mechanisms and targets in the heart"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4480-9341","authenticated-orcid":false,"given":"Maggie S","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, 7 Divinity Ave, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard T","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, 7 Divinity Ave, Cambridge, MA 02138, USA"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-5180","authenticated-orcid":false,"given":"Jessica C","family":"Garbern","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biology and the Harvard Stem Cell Institute, Harvard University, 7 Divinity Ave, Cambridge, MA 02138, USA"},{"name":"Department of Cardiology, Boston Children\u2019s Hospital, 300 Longwood Ave, Boston, MA 02115, 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