Effects of aging on mitochondrial hydrogen peroxide emission and calcium retention capacity in rat heart

Abstract

Aging is a risk factor for heart disease and heart failure, which result from a progressive impairment of cardiac functions, including stroke volume, cardiac output, blood flow, and oxygen consumption. Age-related cardiac dysfunction is associated with impaired cardiac structures, such as the loss of myocytes, structural remodeling, altered calcium (Ca2+) handling, and contractile dysfunction. However, the mechanism by which aging affects mitochondrial function in the heart is poorly understood. The purpose of this study was to determine the effects of aging on mitochondrial function in the rat heart. Male Fischer 344 rats were randomly assigned to very young sedentary (VYS, 1 month), young sedentary (YS, 4 months), middle-aged sedentary (MS, 10 months), and old sedentary (OS, 20 months) groups. mitochondrial complex protein levels and mitochondrial function (e.g., mitochondrial hydrogen peroxide (H2O2) emission and Ca2+ retention capacity) were analyzed in the left ventricle. Aging was associated with decreased levels of OXPHOS (oxidative phosphorylation) protein expression of complex I to IV in the function of the electron transport chain. Aging increased the mitochondrial H2O2 emitting potential in the heart. In contrast, mitochondrial Ca2+ retention capacity gradually decreased with age. These data demonstrate that aging impairs mitochondrial function in cardiac muscle, suggesting that mitochondrial dysfunction with aging may be a primary factor for aging-induced cardiac dysfunction in the heart.

Aging Promotes Mitochondria-Mediated Apoptosis in Rat Hearts

“…These signals eventually result in DNA fragmentation and programmed cell death [12,16,25]. We recently found increased mitochondrial hydrogen peroxide production with aging in rat cardiac muscles [5]. Interestingly, the current study revealed that the Bax/Bcl-2 ratio was markedly higher in the cardiac muscles of older rats, indicating that the aging phase was related to early-stage mitochondria-mediated apoptosis.…”

“…Several studies suggested that mitochondria have evolved to regulate other cellular functions, including those contributing to biological aging, such as the generation of reactive oxygen species (ROS), inflammation, senescence, and resultant necrotic and apoptotic cell death [4]. Our studies have revealed that aging mainly results in damage to the electron transport chain during mitochondrial respiration, due to a decrease in electron transport by complex II-IV, which can promote electron leakage and ROS production [5].…”

“…The mitochondrial Ca 2+ -retention capacity is commonly used to evaluate the susceptibility of mPTP opening sensitivity, as previously reported [5]. The mPTP opening was determined through the Ca 2+ -retention capacity graph.…”

Effects of Acute Exercise on Mitochondrial Function, Dynamics, and Mitophagy in Rat Cardiac and Skeletal Muscles

“…Mitochondrial ROS is generated by products of the mitochondrial electron transfer chain during coupled respiration in complexes I and III [ 15 ]. ROS plays different biological roles depending on its concentration: (1) appropriate ROS is an essential mediator of cellular signaling and redox signals that are necessary for cellular homeostasis [ 16 ]; (2) a low level of ROS is needed for cellular differentiation, proliferation, growth, and adaptive responses [ 17 ]; (3) excessive ROS production induces both mitochondrial dysfunction and oxidative stress in proteins, nuclear DNA, mtDNA, and lipids [ 16 ]. In previous studies, regular exercise reduced ROS and elevated antioxidant enzymes in isolated heart mitochondria [ 10 ] and skeletal muscle [ 7 ].…”

Altered Intracellular Calcium Homeostasis and Arrhythmogenesis in the Aged Heart

“…On the contrary, inhibition of mitochondrial Ca 2+ influx attenuated pro-arrhythmic activity in this model and reduced mitochondrial ROS emission. In pathophysiology, it would be rational to reduce mitochondrial Ca 2+ influx, despite some evidence that SR-mitochondria communication may be diminished in aging [58,63,155]. This reduction may be viewed as an adaptive mechanism to reduce mitochondrial [Ca 2+ ] and, thereby, limit deleterious mitochondrial ROS production in the senescent myocardium.…”