Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging
- Globally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriureticGlobally, cardiovascular diseases are the leading cause of death in the aging population. While the clinical pathology of the aging heart is thoroughly characterized, underlying molecular mechanisms are still insufficiently clarified. The aim of the present study was to establish an in vitro model system of cardiomyocyte premature senescence, culturing heart muscle cells derived from neonatal C57Bl/6J mice for 21 days. Premature senescence of neonatal cardiac myocytes was induced by prolonged culture time in an oxygen-rich postnatal environment. Age-related changes in cellular function were determined by senescence-associated beta-galactosidase activity, increasing presence of cell cycle regulators, such as p16, p53, and p21, accumulation of protein aggregates, and restricted proteolysis in terms of decreasing (macro-)autophagy. Furthermore, the culture system was functionally characterized for alterations in cell morphology and contractility. An increase in cellular size associated with induced expression of atrial natriuretic peptides demonstrated a stress-induced hypertrophic phenotype in neonatal cardiomyocytes. Using the recently developed analytical software tool Myocyter, we were able to show a spatiotemporal constraint in spontaneous contraction behavior during cultivation. Within the present study, the 21-day culture of neonatal cardiomyocytes was defined as a functional model system of premature cardiac senescence to study age-related changes in cardiomyocyte contractility and autophagy.…
Author details: | Steffen HäseliORCiD, Stefanie Deubel, Tobias JungORCiDGND, Tilman GruneORCiDGND, Christiane OttORCiDGND |
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DOI: | https://doi.org/10.1155/2020/8141307 |
ISSN: | 1942-0994 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/32377307 |
Title of parent work (English): | Oxidative medicine and cellular longevity |
Publisher: | Landes Bioscience |
Place of publishing: | Austin, Tex. |
Publication type: | Article |
Language: | English |
Date of first publication: | 2020/04/15 |
Publication year: | 2020 |
Release date: | 2023/11/10 |
Volume: | 2020 |
Issue: | Special Issue |
Article number: | 8141307 |
Number of pages: | 14 |
Funding institution: | German Research Council (DFG)German Research Foundation (DFG) [GR; 1240/22-1]; Ministry of Science of the State of Brandenburg; German; Center for Cardiovascular Research (DZHK); German Ministry of Education; and Research (BMBF)Federal Ministry of Education & Research (BMBF); German Institute of Human Nutrition Potsdam-Rehbrucke (DIfE) |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC classification: | 5 Naturwissenschaften und Mathematik / 50 Naturwissenschaften / 500 Naturwissenschaften und Mathematik |
Peer review: | Referiert |
Publishing method: | Open Access / Gold Open-Access |
DOAJ gelistet | |
License (German): | CC-BY - Namensnennung 4.0 International |