Cardiac ageing manifests as a decline in function leading to heart failure. At the cellular level, ageing entails decreased replicative capacity and dysregulation of cellular processes in myocardial and nonmyocyte cells. Various extrinsic parameters, such as lifestyle and environment, integrate important signalling pathways, such as those involving inflammation and oxidative stress, with intrinsic molecular mechanisms underlying resistance versus progression to cellular senescence. Mitigation of cardiac functional decline in an ageing organism requires the activation of enhanced maintenance and reparative capacity, thereby overcoming inherent endogenous limitations to retaining a youthful phenotype. Deciphering the molecular mechanisms underlying dysregulation of cellular function and renewal reveals potential interventional targets to attenuate degenerative processes at the cellular and systemic levels to improve quality of life for our ageing population. In this Review, we discuss the roles of extrinsic and intrinsic factors in cardiac ageing. Animal models of cardiac ageing are summarized, followed by an overview of the current and possible future treatments to mitigate the deleterious effects of cardiac ageing.
Ageing is a primary risk factor for cardiovascular disease and mortality.
The capacity of the adult human heart to maintain function and preserve cellular homeostasis declines with age.
Extrinsic factors of environment, behaviour, and lifestyle can promote or blunt cellular and molecular cardiac ageing.
Intrinsic processes that promote cellular ageing, such as inflammation and oxidative stress, exacerbate telomere shortening, chromatin remodelling, and epigenetic drift.
Cardiovascular ageing is inextricably tied to genetic predisposition and the complex interaction of hereditary influences.
Promising advances to antagonize myocardial ageing connect external factors with intrinsic molecular mechanisms, enabling interventional strategies on both behavioural and cellular levels.
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N.A.G. is supported by NIH grants R37HL091102, R01HL117163, R01HL105759, and U54CA132384. K.M.B. is supported by NIH grant F32HL136196. M.A.S. is supported by NIH grants R01HL067245, R37HL091102, R01HL105759, R01HL113647, R01HL117163, P01HL085577, and R01HL122525, as well as by an award from the Fondation Leducq.
K.M.B. has a significant interest in CardioCreate, and M.A.S. is a founding member of CardioCreate. N.A.G. and F.F. declare no competing interests.
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Atlas of Gene Expression in Mouse Aging Project (AGEMAP): https://omictools.com/atlas-of-gene-expression-in-mouse-aging-project-tool
Database of Genotypes and Phenotypes (dbGaP): https://www.ncbi.nlm.nih.gov/gap
Digital Ageing Atlas (DAA): http://ageing-map.org/
Human Ageing Genomic Resources (HAGR): http://genomics.senescence.info/
JenAge Ageing Factor Database (AgeFactDB): http://agefactdb.jenage.de/
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Gude, N.A., Broughton, K.M., Firouzi, F. et al. Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence. Nat Rev Cardiol 15, 523–542 (2018). https://doi.org/10.1038/s41569-018-0061-5
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