PUBLICATION
Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish
- Authors
- Murphy, L.B., Santos-Ledo, A., Dhanaseelan, T., Eley, L., Burns, D., Henderson, D.J., Chaudhry, B.
- ID
- ZDB-PUB-210729-6
- Date
- 2021
- Source
- Disease models & mechanisms 14(7): (Journal)
- Registered Authors
- Chaudhry, Bill
- Keywords
- Aging, Cardiomyocyte turnover, Exercise, Fibrosis, Zebrafish heart
- MeSH Terms
-
- Aging/physiology
- Animals
- Apoptosis
- Cell Proliferation
- Heart/physiology
- Myocytes, Cardiac*/metabolism
- Zebrafish*/metabolism
- PubMed
- 34296752 Full text @ Dis. Model. Mech.
Citation
Murphy, L.B., Santos-Ledo, A., Dhanaseelan, T., Eley, L., Burns, D., Henderson, D.J., Chaudhry, B. (2021) Exercise, programmed cell death and exhaustion of cardiomyocyte proliferation in aging zebrafish. Disease models & mechanisms. 14(7):.
Abstract
Exercise may ameliorate the eventual heart failure inherent in human aging. In this study, we use zebrafish to understand how aging and exercise affect cardiomyocyte turnover and myocardial remodelling. We show that cardiomyocyte proliferation remains constant throughout life but that onset of fibrosis is associated with a late increase in apoptosis. These findings correlate with decreases in voluntary swimming activity, critical swimming speed (Ucrit), and increases in biomarkers of cardiac insufficiency. The ability to respond to severe physiological stress is also impaired with age. Although young adult fish respond with robust cardiomyocyte proliferation in response to enforced swimming, this is dramatically impaired in older fish and served by a smaller proliferation-competent cardiomyocyte population. Finally, we show that these aging responses can be improved through increased activity throughout adulthood. However, despite improvement in Ucrit and the proliferative response to stress, the size of the proliferating cardiomyocyte population remained unchanged. The zebrafish heart models human aging and reveals the important trade-off between preserving cardiovascular fitness through exercise at the expense of accelerated fibrotic change.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping