Regulatory Mechanisms of Mitochondrial Function and Cardiac Aging

Abstract

Aging is a major risk factor for cardiovascular diseases (CVDs), the major cause of death worldwide. Cardiac myocytes, which hold the most abundant mitochondrial population, are terminally differentiated cells with diminished regenerative capacity in the adult. Cardiomyocyte mitochondrial dysfunction is a characteristic feature of the aging heart and one out of the nine features of cellular aging. Aging and cardiac pathologies are also associated with increased senescence in the heart. However, the cause and consequences of cardiac senescence during aging or in cardiac pathologies are mostly unrecognized. Further, despite recent advancement in anti-senescence therapy, the targeted cell type and the effect on cardiac structure and function have been largely overlooked. The unique cellular composition of the heart, and especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging. Here we review recent findings regarding key factors regulating cell senescence, mitochondrial health as well as cardiomyocyte rejuvenation.

Mitochondrial Dysfunction and Inflammaging in Heart Failure: Novel Roles of CYP-Derived Epoxylipids

“…Aged cardiomyocytes show extensive mitochondrial abnormalities, including enlarged structure, loss of cristae, reduction in ATP synthesis, impaired dynamics and increased ROS production [ 40 , 79 , 86 , 89 ]. Historically, numerous studies have proposed the detrimental alterations in mitochondrial function and structure play a central role in myocardial hypertrophy, fibrosis and consequently transition to HF [ 90 , 91 ]. The role mitochondria have in activating NLRP-3 inflammasomes has led to new concepts for their involvement in aging and age-related diseases and mitochondria-induced inflammasome activation has become central to theories of cardiac aging [ 29 , 92 , 93 ].…”

The Effects of Resveratrol on Telomeres and Post Myocardial Infarction Remodeling

“…Senolysis could reverse aging-related cardiovascular pathologies without potential for tumorigenesis [ 18 ]. Cardiac myocytes ( have the most abundant mitochondrial population ) are terminally differentiated cells with low regenerative capacity in the adult [ 19 ]. Cardiomyocyte mitochondrial dysfunction is a main feature of the aging heart [ 19 ].…”

“…Cardiac myocytes ( have the most abundant mitochondrial population ) are terminally differentiated cells with low regenerative capacity in the adult [ 19 ]. Cardiomyocyte mitochondrial dysfunction is a main feature of the aging heart [ 19 ]. Lin et al studied aging and cardiac pathologies in association with increased senescence in the heart [ 19 ].…”

“…Cardiomyocyte mitochondrial dysfunction is a main feature of the aging heart [ 19 ]. Lin et al studied aging and cardiac pathologies in association with increased senescence in the heart [ 19 ]. The unique cellular composition of the heart, especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging [ 19 ].…”

“…Lin et al studied aging and cardiac pathologies in association with increased senescence in the heart [ 19 ]. The unique cellular composition of the heart, especially the functional properties of cardiomyocytes, need to be considered when designing therapeutics to target cardiac aging [ 19 ]. They reviewed recent findings regarding key factors regulating cell senescence, mitochondrial health as well as cardiomyocyte rejuvenation [ 19 ].…”