Abstract
Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis). These events eventually lead to cardiac remodeling and failure. Senescent cardiomyocytes show the hallmarks of DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile dysfunction, hypertrophic growth, and senescence-associated secreting phenotype (SASP). Metabolism within cardiomyocytes is essential not only to fuel the pump function of the heart but also to maintain the functional homeostasis and participate in the senescence of cardiomyocytes. The senescence of cardiomyocyte is also regulated by the non-myocytes (endothelial cells, fibroblasts, and immune cells) in the local microenvironment. On the other hand, the senescent cardiomyocytes alter their phenotypes and subsequently affect the non-myocytes in the local microenvironment and contribute to cardiac aging and pathological remodeling. In this review, we first summarized the hallmarks of the senescence of cardiomyocytes. Then, we discussed the metabolic switch within senescent cardiomyocytes and provided a discussion of the cellular communications between dysfunctional cardiomyocytes and non-myocytes in the local microenvironment. We also addressed the functions of metabolic regulators within non-myocytes in modulating myocardial microenvironment. Finally, we pointed out some interesting and important questions that are needed to be addressed by further studies.
Highlights
Cardiovascular diseases (CVDs), including cardiomyopathy, heart failure, hypertension, and atherosclerosis, have become the leading cause of death worldwide [1]
The heart is an organ with high energy demand, and the metabolic pattern of cardiomyocytes is different from the local non-myocytes [3]
Metabolic homeostasis is very important for the development and physiological function of cardiomyocytes
Summary
Cardiovascular diseases (CVDs), including cardiomyopathy, heart failure, hypertension, and atherosclerosis, have become the leading cause of death worldwide [1]. The increased senescence of cardiomyocytes centrally contributes to cardiac aging, dysfunction, and failure. The heart is an organ with high energy demand, and the metabolic pattern of cardiomyocytes is different from the local non-myocytes [3]. During aging and cardiac stress, the alteration in the metabolism of the myocardial tissues is common, which is essentially involved in functional defects of the heart [8, 9]. Alteration of metabolism pattern contributes to the senescence of cardiomyocytes and cardiac aging [10]. The dysfunction of nonmyocytes in the aged and stressed myocardial tissues facilitates the dysfunction and senescence of cardiomyocytes, enhancing the progress of cardiac diseases [9, 12,13,14,15,16]. We will discuss the hallmarks of cardiomyocyte senescence and metabolic modification of senescent cardiomyocytes and the cellular communications within the local microenvironment
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