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 Ca2+ 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.
Highlights
Myocardial systolic and diastolic function diminish with age, contributing to high morbidity and mortality of cardiovascular diseases (CVDs) in the elderly [1]
This review focuses on cardiac contractility changes and the underlying mechanism during aging
A study focusing on Hutchinson-Gilford progeria syndrome (HGPS) revealed that a LMNA mutation is up-regulated in the aging process
Summary
Myocardial systolic and diastolic function diminish with age, contributing to high morbidity and mortality of cardiovascular diseases (CVDs) in the elderly [1]. An opposite result of SERCA2a expression was recently reported on atrioventricular junction of 24-month-old Wistar rats [40] This finding suggested to us that the Ca2+ transient might be different in each part of the heart during aging, which may involve aging contractility compensatory mechanisms. Expression of RyR, the major protein involved in SR Ca2+ release, is reported to have an ageassociated reduction [27]; the RyRs are overactivated by over-oxidized CaMKII and PKA in aged hearts, resulting in an enhanced diastolic Ca2+ leak and decreased SR Ca2+ storage [48]. Together with reduced expression of SERCA2, the aged heart has delayed and weaker peak contractions at higher stimulation frequencies [37] and causes contractile dysfunction [49,50]. The attenuated recovery of Ca2+ homeostasis by ROS-induced over activated RyR is one of the potential reasons for AVV1/SERCA2a therapy inefficiency
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