Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease
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 a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1558 |
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| author | Eleonora Cianflone Michele Torella Flavia Biamonte Antonella De Angelis Konrad Urbanek Francesco S. Costanzo Marcello Rota Georgina M. Ellison-Hughes Daniele Torella |
| author_facet | Eleonora Cianflone Michele Torella Flavia Biamonte Antonella De Angelis Konrad Urbanek Francesco S. Costanzo Marcello Rota Georgina M. Ellison-Hughes Daniele Torella |
| author_sort | Eleonora Cianflone |
| collection | DOAJ |
| description | 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/p16<sup>INK4</sup>/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. |
| first_indexed | 2024-03-10T18:52:29Z |
| format | Article |
| id | doaj.art-89909e662c0349e39767d85c0a696bd3 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:52:29Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-89909e662c0349e39767d85c0a696bd32023-11-20T05:03:57ZengMDPI AGCells2073-44092020-06-0196155810.3390/cells9061558Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and DiseaseEleonora Cianflone0Michele Torella1Flavia Biamonte2Antonella De Angelis3Konrad Urbanek4Francesco S. Costanzo5Marcello Rota6Georgina M. Ellison-Hughes7Daniele Torella8Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Translational Medical Sciences, AORN dei Colli/Monaldi Hospital, University of Campania “L. Vanvitelli”, Via Leonardo Bianchi, 80131 Naples, ItalyDepartment of Experimental and Clinical Medicine and Interdepartmental Centre of Services (CIS), Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Experimental Medicine, Section of Pharmacology, University of Campania “L.Vanvitelli”, 80121 Naples, ItalyMolecular and Cellular Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Experimental and Clinical Medicine and Interdepartmental Centre of Services (CIS), Magna Graecia University, 88100 Catanzaro, ItalyDepartment of Physiology, New York Medical College, Valhalla, NY 10595, USACentre 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, UKMolecular and Cellular Cardiology, Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, ItalyAdult 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/p16<sup>INK4</sup>/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.https://www.mdpi.com/2073-4409/9/6/1558senescenceagingadult stem cellstissue homeostasisepigeneticsmetabolism |
| spellingShingle | Eleonora Cianflone Michele Torella Flavia Biamonte Antonella De Angelis Konrad Urbanek Francesco S. Costanzo Marcello Rota Georgina M. Ellison-Hughes Daniele Torella Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease Cells senescence aging adult stem cells tissue homeostasis epigenetics metabolism |
| title | Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease |
| title_full | Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease |
| title_fullStr | Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease |
| title_full_unstemmed | Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease |
| title_short | Targeting Cardiac Stem Cell Senescence to Treat Cardiac Aging and Disease |
| title_sort | targeting cardiac stem cell senescence to treat cardiac aging and disease |
| topic | senescence aging adult stem cells tissue homeostasis epigenetics metabolism |
| url | https://www.mdpi.com/2073-4409/9/6/1558 |
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