Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival
Open accessAbstract
Cardiac muscle regeneration after injury is limited by “irreversible” cell cycle exit. Telomere shortening is one postulated basis for replicative senescence, via down-regulation of telomerase reverse transcriptase (TERT); telomere dysfunction also is associated with greater sensitivity to apoptosis. Forced expression of TERT in cardiac muscle in mice was sufficient to rescue telomerase activity and telomere length. Initially, the ventricle was hypercellular, with increased myocyte density and DNA synthesis. By 12 wk, cell cycling subsided; instead, cell enlargement (hypertrophy) was seen, without fibrosis or impaired function. Likewise, viral delivery of TERT was sufficient for hypertrophy in cultured cardiac myocytes. The TERT virus and transgene also conferred protection from apoptosis, in vitro and in vivo . Hyperplasia, hypertrophy, and survival all required active TERT and were not seen with a catalytically inactive mutation. Thus, TERT can delay cell cycle exit in cardiac muscle, induce hypertrophy in postmitotic cells, and promote cardiac myocyte survival.
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The most persuasive evidence for a causal role comes from in vitro and in vivo manipulation of telomerase activity which impacts on TL and has been shown to enhance or reverse senescence and ageing-associated phenotypes.
“The most persuasive evidence for a causal role comes from in vitro and in vivo manipulation of telomerase activity which impacts on TL and has been shown to enhance or reverse senescence and ageing-associated phenotypes35–39.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [36]
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- Authors
- Oh, H., Taffet, G. E., Youker, K. A., Entman, M. L., Overbeek, P. A., Michael, L. H., & Schneider, M. D.
- Affiliations
- Baylor College of Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2001-08-21
- Volume
- 98
- Issue
- 18
- Pages
- 10308-10313
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC56957
- OpenAlex
- W2086007966
- Cited by
- 289
- References
- 42
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 14 · 2017: 12 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 13 · 2012: 12
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- telomerase reverse transcriptase, cardiomyocytes, cardiomyocyte hypertrophy, cardiomyocyte proliferation, cell cycle exit, replicative senescence, telomere shortening, apoptosis resistance, cardiac regeneration, viral gene delivery
- MeSH terms
- Animals, Base Sequence, Cell Division, Cell Survival, Cells, Cultured, DNA-Binding Proteins, Cardiomegaly, Humans, Mice, Transgenic, Myocardium, Telomere, Apoptosis, DNA Primers, Gene Expression Regulation, Developmental, Telomerase, Cell Size, Mice, Rats
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