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Open AccessReview

Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease

1
Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
2
Department of Translational Medical Sciences, AORN dei Colli/Monaldi Hospital, University of Campania “L. Vanvitelli”, Via Leonardo Bianchi, 80131 Naples, Italy
3
Department of Experimental and Clinical Medicine and Interdepartmental Centre of Services (CIS), Magna Graecia University, 88100 Catanzaro, Italy
4
Department of Experimental Medicine, Section of Pharmacology, University of Campania “L.Vanvitelli”, 80121 Naples, Italy
5
Molecular and Cellular Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy
6
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA
7
Centre for Human and Applied Physiological Sciences and Centre for Stem Cells and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guys Campus-Great Maze Pond rd, London SE1 1UL, UK
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(6), 1558; https://doi.org/10.3390/cells9061558
Received: 1 June 2020 / Revised: 19 June 2020 / Accepted: 25 June 2020 / Published: 26 June 2020
Adult stem/progenitor are a small population of cells that reside in tissue-specific niches and possess the potential to differentiate in all cell types of the organ in which they operate. Adult stem cells are implicated with the homeostasis, regeneration, and aging of all tissues. Tissue-specific adult stem cell senescence has emerged as an attractive theory for the decline in mammalian tissue and organ function during aging. Cardiac aging, in particular, manifests as functional tissue degeneration that leads to heart failure. Adult cardiac stem/progenitor cell (CSC) senescence has been accordingly associated with physiological and pathological processes encompassing both non-age and age-related decline in cardiac tissue repair and organ dysfunction and disease. Senescence is a highly active and dynamic cell process with a first classical hallmark represented by its replicative limit, which is the establishment of a stable growth arrest over time that is mainly secondary to DNA damage and reactive oxygen species (ROS) accumulation elicited by different intrinsic stimuli (like metabolism), as well as external stimuli and age. Replicative senescence is mainly executed by telomere shortening, the activation of the p53/p16INK4/Rb molecular pathways, and chromatin remodeling. In addition, senescent cells produce and secrete a complex mixture of molecules, commonly known as the senescence-associated secretory phenotype (SASP), that regulate most of their non-cell-autonomous effects. In this review, we discuss the molecular and cellular mechanisms regulating different characteristics of the senescence phenotype and their consequences for adult CSCs in particular. Because senescent cells contribute to the outcome of a variety of cardiac diseases, including age-related and unrelated cardiac diseases like diabetic cardiomyopathy and anthracycline cardiotoxicity, therapies that target senescent cell clearance are actively being explored. Moreover, the further understanding of the reversibility of the senescence phenotype will help to develop novel rational therapeutic strategies. View Full-Text
Keywords: senescence; aging; adult stem cells; tissue homeostasis; epigenetics; metabolism; SASP senescence; aging; adult stem cells; tissue homeostasis; epigenetics; metabolism; SASP
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MDPI and ACS Style

Cianflone, E.; Torella, M.; Biamonte, F.; De Angelis, A.; Urbanek, K.; Costanzo, F.S.; Rota, M.; Ellison-Hughes, G.M.; Torella, D. Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease. Cells 2020, 9, 1558. https://doi.org/10.3390/cells9061558

AMA Style

Cianflone E, Torella M, Biamonte F, De Angelis A, Urbanek K, Costanzo FS, Rota M, Ellison-Hughes GM, Torella D. Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease. Cells. 2020; 9(6):1558. https://doi.org/10.3390/cells9061558

Chicago/Turabian Style

Cianflone, Eleonora; Torella, Michele; Biamonte, Flavia; De Angelis, Antonella; Urbanek, Konrad; Costanzo, Francesco S.; Rota, Marcello; Ellison-Hughes, Georgina M.; Torella, Daniele. 2020. "Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease" Cells 9, no. 6: 1558. https://doi.org/10.3390/cells9061558

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