Cardiac Physiology of Aging: Extracellular Considerations

Abstract

Aging is a major risk factor for the development of cardiovascular disease, with the majority of affected patients being elderly. Progressive changes to myocardial structure and function occur with aging, often in concert with underlying pathologies. However, whether chronological aging results in a remodeled "aged substrate" has yet to be established. In addition to myocyte contractility, myocardial performance relies heavily on the cardiac extracellular matrix (ECM), the roles of which are as dynamic as they are significant; including providing structural integrity, assisting in force transmission throughout the cardiac cycle and acting as a signaling medium for communication between cells and the extracellular environment. In the healthy heart, ECM homeostasis must be maintained, and matrix deposition is in balance with degradation. Consequently, alterations to, or misregulation of the cardiac ECM has been shown to occur in both aging and in pathological remodeling with disease. Mounting evidence suggests that age-induced matrix remodeling may occur at the level of ECM control; including collagen synthesis, deposition, maturation, and degradation. Furthermore, experimental studies using aged animal models not only suggest that the aged heart may respond differently to insult than the young, but the identification of key players specific to remodeling with age may hold future therapeutic potential for the treatment of cardiac dysfunction in the elderly. This review will focus on the role of the cardiac interstitium in the physiology of the aging myocardium, with particular emphasis on the implications to age-related remodeling in disease.

Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1‐mediated autophagy regulation

“…Biological aging is an irreversible process featured by progressive myocardial remodeling, reduced cardiac reserve, diastolic dysfunction, and a higher cardiac morbidity and mortality in the elderly (Lakatta, ; Sussman & Anversa, ; Yang et al ., ; Shimizu & Minamino, ). A number of hypotheses have been postulated for cardiac aging including oxidative stress, depletion of cellular fuel, myosin heavy chain isozyme switch, apoptosis, mitochondrial injury, autophagy dysregulation, and intracellular Ca 2+ mishandling (Lakatta, ; Yang et al ., , ; Boengler et al ., ; Feridooni et al ., ; Horn, ). Nonetheless, the precise machineries behind cardiac aging still remain somewhat elusive.…”

Mechanical Regulation of Cardiac Aging in Model Systems

“…68-70 These changes impact cardiomyocyte function, 71 not only by changing the mechanical properties of the tissue, but also by altering transmembrane receptors. 72-74 Cardiac ECM has been recently reviewed, 75-77 so we will focus on compositional changes that have been implicated in switching from adaptive to maladaptive remodeling (Figure 2, top). On the opposing side of the sarcolemma (Figure 2, bottom), costameres aid in cell-ECM adhesion by adhering Z-discs to ECM.…”

Left ventricular untwist in healthy children and adolescents born full-term

“…Согласно данным литературы, процессы созревания миокарда у ребенка подразумевают повышение способности миокарда сокращаться вследствие увеличения количества и организации миофиламентов, созревания саркоплазматического ретикулума, активизации Са 2+ -АТФазы, повышения чувствительности к кальцию, оптимизации состояния рианодиновых рецепторов, изменения функции сарколемных насосов, каналов в сократительных белках [41,42], а также оптимальное состояние сердечного внеклеточного матрикса, процессов синтеза, созревания и деградации коллагена [43,44]. В клинических исследованиях описана корреляционная связь между содержанием изоформы N2B титина и параметрами апикального раскручивания у человека [7,45].…”