Cardiac ageing: extrinsic and intrinsic factors in cellular renewal and senescence

Abstract

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.

Aging induces cardiac mesenchymal stromal cell senescence and promotes endothelial cell fate of the CD90 + subset

“…In diverse organs, a better understanding of stroma heterogeneity and locally produced microenvironmental factors has revealed key roles for non parenchymal cells in tissue homeostasis (Gude, Broughton, Firouzi, & Sussman, ). Of the structural modifications classically observed in the aging heart, such as perivascular fibrosis, cardiomyocyte hypertrophy, microvascular rarefaction, and increased tortuosity of coronary vessels (Han, ; Pries et al, ), many are caused by stroma cells or interactions between stroma and parenchymal cells.…”

Imbalance of ER and Mitochondria Interactions: Prelude to Cardiac Ageing and Disease?

“…Ageing is a primary risk factor for cardiac disease [56]. Cardiac ageing manifests as a decline in structure and function of the heart, leading to cardiac disease [57,58]. At the cellular level, ageing entails a decline in mitochondrial function and dysregulation of cellular processes, such as oxidative stress, autophagy, and metabolic imbalance, in cardiomyocytes [57].…”

“…Cardiac ageing manifests as a decline in structure and function of the heart, leading to cardiac disease [57,58]. At the cellular level, ageing entails a decline in mitochondrial function and dysregulation of cellular processes, such as oxidative stress, autophagy, and metabolic imbalance, in cardiomyocytes [57]. Mitochondrial alterations, including impaired metabolism and metabolic flexibility with a decreased capacity to oxidize fatty acids and enhanced dependence on glucose metabolism, are critically involved in increased sensitivity to stress in the aged heart [59].…”

Adaptation within embryonic and neonatal heart environment reveals alternative fates for adult c-kit+ cardiac interstitial cells

“…Biological activities of CIC continue to defy simple categorization, due in part to the heterogeneous nature of the population as well as inherent plasticity of individual cells . CICs participate in all aspects of myocardial biology from development to maturation, homeostasis to aging, and acute injury to chronic remodeling . Regulatory functions of CICs in critical aspects of cardiac biology have spawned multiple approaches to influence their properties and activity with the goal of promoting beneficial action and mitigating maladaptive influences.…”

“…Myocardial homeostasis is maintained by dynamic interaction on multiple levels between cardiomyocytes and the cardiac interstitial cell (CIC) population. Decades of study reveals CICs as a heterogeneous collection of cell types that defy simple categorization, due in part to their fluid adaptability in response to development, aging, acute injury, and chronic stress . Parsing out CIC subtypes with specific markers such as periostin or Tcf21 has merged with the more impartial and nuanced approach of transcriptomic profiling at the single cell level .…”