Aging Attenuates Cardiac Contractility and Affects Therapeutic Consequences for Myocardial Infarction

Abstract

Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca 2+ transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.

Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility

“…AMPK, as a central cellular sensor of energy metabolism, plays an important role in the regulation of myocardial signaling and contractile function in the aging heart (Dong et al, 2020;Turdi et al, 2010;Zaha et al, 2016). To further delineate whether the impaired AMPK activation caused by defected SIRT1 and SIRT3 precedes myocardial contractile dysfunction in the aged heart during I/R, we proposed to evaluate the contractile properties of isolated cardio- The contractile properties of the isolated cardiomyocytes from young/aged WT, SIRT1 f/f /icSIRT1 −/− , and SIRT3 f/f /cSIRT3 −/− hearts under normoxia and H/R stress conditions.…”

“…I/R stress is known to induce greater injury in the aged heart with no effective treatment strategy (Dong et al, 2020). The study demonstrated that both SIRT1 and SIRT3 were decreased with cardiac aging and age‐related deficiency of SIRT1 and SIRT3 plays critical role in maintaining cardiac function and cardiomyocyte contractile function in response to I/R stress.…”

Effects of Aging on Hemodynamic Kinetics in Different Intensities of Dynamic Exercise

“…To contrast, this is the first study to evaluate such measurements in young and old humans. While substantial evidence obtained from cardiac muscle tissue alone has indicated relatively small age-related changes in intrinsic cardiac muscle function [28], the efficacy of beta-adrenergic stimulation of HR, myocardial contractility, and arterial vascular tone decrease with advancing age [28][29][30]. It has been hypothesized that changes in cardiovascular performance with advancing age may be partially explained on this basis [28].…”

New Developments in Exosomal lncRNAs in Cardiovascular Diseases

“…Aging leads to excessive oxidative stress, chronic low-grade inflammation, telomere shortening, autophagy, and mitochondrial dysfunction (90)(91)(92). Aging also mediates communication between cardiomyocytes and endothelial cells, fibroblasts, and immune cells (93) and promotes vascular wall endothelial damage, atherosclerosis, myocardial fibrosis, coronary heart disease, and heart failure (94,95). Currently, the strategies applied to delay cardiac aging include repairing mitochondrial dysfunction (96), targeting cardiac stem cell senescence and senescence-associated secretory phenotype changes (97), inducing autophagy (90), and hydrogen sulfidemediated regulation of senescence signals (98).…”