Proteostasis in cardiac health and disease
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Updated: Feb 27, 2026
Isolation and Physiological Analysis of Mouse Cardiomyocytes
Published on: September 7, 2014
Robert H Henning1, Bianca J J M Brundel2
1Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Insights
As people age, cardiac diseases increase due to declining protein quality control. Maintaining protein homeostasis in the heart offers a new strategy to combat cardiac aging and disease.
Area of Science:
- Cardiovascular Science
- Gerontology
- Molecular Biology
Background:
- Cardiac diseases are a leading cause of death globally, with incidence projected to rise due to population aging.
- Cellular aging is linked to the breakdown of protein homeostasis (proteostasis) and impaired protein quality control.
- In the heart, accumulated protein damage can overwhelm quality control mechanisms, accelerating cardiac aging.
Purpose of the Study:
- To explore the role of protein quality control in cardiac aging.
- To identify therapeutic strategies targeting proteostasis for cardiac health.
- To investigate the link between protein homeostasis and cardiomyocyte senescence.
Main Methods:
- Review of prevailing theories on aging mechanisms.
- Analysis of factors contributing to protein quality control failure in the heart.
- Examination of the relationship between impaired proteostasis and cardiomyocyte senescence.
Main Results:
- Loss of protein patency, due to genetic or environmental factors, overwhelms cardiac protein quality control.
- Failure involves impaired chaperones, ubiquitin-proteasomal systems, and autophagy, leading to protein aggregation.
- This failure contributes to cardiomyocyte senescence and cardiac aging.
Conclusions:
- Maintaining cardiac proteostasis by targeting protein quality control is a novel therapeutic strategy.
- This approach holds promise for promoting cardiac health and combating age-related cardiac diseases.
- Existing drugs can be explored for clinical application of this strategy.
Abstract:
The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.
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