Journal article 136 views 4 downloads
Senescence-related myocardial dysfunction: keeping a young heart
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Robert T R Huckstepp ,
Naveed Akbar ,
Johann Bauersachs ,
Jesher Ching Wai Lok,
Juel Choppy-Madeleine,
Gary Christopher ,
Mayank Dalakoti ,
Emily Dawson-Plincke,
John Dodds,
Georgina M Ellison-Hughes ,
Costanza Emanueli ,
Christopher George ,
Anushka Goyal,
Victoria Higginbotham,
Lorenz Holzner,
Venkat Kanamarlapudi ,
Paolo Madeddu ,
Claudio Mauro ,
Fiona Lewis-McDougall ,
Andrew J Murray ,
Renita Peter Damien Genetus,
Emma Short ,
Mark A Sussman ,
Adriana A S Tavares ,
Samuel Thompson,
Morya Wadodkar,
Stuart R G Calimport ,
Barry L Bentley ,
Victoria Higginbotham
European Heart Journal
Swansea University Authors:
Gary Christopher , Christopher George , Venkat Kanamarlapudi , Victoria Higginbotham
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© The Author(s) 2026. This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
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DOI (Published version): 10.1093/eurheartj/ehag095
Abstract
The heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the...
| Published in: | European Heart Journal |
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| ISSN: | 0195-668X 1522-9645 |
| Published: |
Oxford University Press (OUP)
2026
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa71384 |
| Abstract: |
The heart, a vital organ, works without interruption and constantly adjusts to the ever-changing demands on our body. It adapts to physiological and pathological changes, including exercise and emotional state, as well as metabolic, respiratory, and vascular abnormalities. The pumping action of the heart is determined by the health of the myocardium, which undergoes changes with ageing that are both under-investigated and incompletely understood, potentially impacting our approach to pathological conditions. Here, the alterations in cellular, tissue, and gross physiological function of the heart with age are discussed. At the molecular level, non-coding RNAs influence cellular senescence, and extracellular vesicles induce fibrosis through matrix remodelling. Mitochondrial dysfunction and altered fatty acid oxidation reduce cellular energetics, whilst accumulation of reactive oxygen species and steatosis, as well as telomere shortening coupled with reduced autophagy, limit the myocardium’s regenerative capability. Loss of cardiomyocytes, combined with senescence, requires compensatory hypertrophy, inducing myocardial stiffness and altered muscle function. In addition to these direct alterations in myocardial characteristics with ageing, other factors that can affect the myocardium indirectly are addressed, including valve calcification, resulting in regurgitation and/or stenosis; vascular abnormalities, reducing compliance and exacerbating hypertension; fibrosis leading to cardiac arrhythmias; and autonomic dysregulation, reducing cardiac adaptability. Finally, potential modulation of cardiac ageing is discussed whilst also addressing which senescent modifications should be considered as ageing-related physiological changes of the myocardium. A better understanding of myocardial ageing will differentiate physiological changes from early, preventable, and reversible pathological changes, consequently helping to optimize management of individuals with or at risk of myocardial disease by taking into account diverse trajectories of myocardial ageing. |
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| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
British Heart Foundation, Health and Care Research Wales, UKRI, Wellcome Trust, BBSRC, Diabetes UK, NIHR, Abbott, EU, Tobacco Related Disease Research Program (US) |