Abstract
Chronological aging as well as biological aging accelerated by various pathologies such as diabetes and obesity contribute to cardiovascular aging, and structural and functional tissue damage of the heart and vasculature. Cardiovascular aging in humans is characterized by structural pathologic remodeling including cardiac and vascular fibrosis, hypertrophy, stiffness, micro- and macro-circulatory impairment, left ventricular diastolic dysfunction precipitating heart failure with either reduced or preserved ejection fraction, and cardiovascular cell death. Cellular senescence, an important hallmark of aging, is a critical factor that impairs repair and regeneration of damaged cells in cardiovascular tissues whereas autophagy, an intracellular catabolic process is an essential inherent mechanism that removes senescent cells throughout life time in all tissues. Several recent reviews have highlighted the fact that all longevity treatment paradigms to mitigate progression of aging-related pathologies converge in induction of autophagy, activation of AMP kinase (AMPK) and Sirtuin pathway, and inhibition of mechanistic target of rapamycin (mTOR). These longevity treatments include health style changes such as caloric restriction, and drug treatments using rapamycin, the first FDA-approved longevity drug, as well as other experimental longevity drugs such as metformin, rapamycin, aspirin, and resveratrol. However, in the heart tissue, autophagy induction has to be tightly regulated since evidence show excessive autophagy results in cardiomyopathy and heart failure. Here we discuss emerging evidence for microRNA-mediated tight regulation of autophagy in the heart in response to treatment with rapamycin, and novel approaches to monitor autophagy progression in a temporal manner to diagnose and regulate autophagy induction by longevity treatments.
Highlights
Global deaths from cardiovascular disease increased by 41% between 1990 and 2013 and population ageing alone contributed to an estimated 52.5% increase in these deaths (Roth et al, 2015; Roth et al, 2018)
cardiovascular diseases (CVD) resulting from a variety of metabolic and environmental stressors or infections promote cellular senescence and accelerate cellular, organ-level, and organismal aging
Left ventricular diastolic dysfunction that precipitates heart failure with reduced or preserved ejection fraction, vascular fibrosis, stiffness, and impairment of synthesis and/or secretion of endothelium-derived vasoactive molecules that underlie atherosclerosis and other vasculopathies mark cardiovascular aging. These cardiovascular pathologies are common to both chronological aging and accelerated biological aging induced by metabolic diseases such as diabetes and obesity despite the differences in the stressors in these different conditions (Ghebre et al, 2016; Upadhya and Kitzman, 2017; Ungvari et al, 2018; Jin, 2019; Wagner and Dimmeler, 2020)
Summary
Global deaths from cardiovascular disease increased by 41% between 1990 and 2013 and population ageing alone contributed to an estimated 52.5% increase in these deaths (Roth et al, 2015; Roth et al, 2018). Left ventricular diastolic dysfunction that precipitates heart failure with reduced or preserved ejection fraction, vascular fibrosis, stiffness, and impairment of synthesis and/or secretion of endothelium-derived vasoactive molecules that underlie atherosclerosis and other vasculopathies mark cardiovascular aging These cardiovascular pathologies are common to both chronological aging and accelerated biological aging induced by metabolic diseases such as diabetes and obesity despite the differences in the stressors in these different conditions (Ghebre et al, 2016; Upadhya and Kitzman, 2017; Ungvari et al, 2018; Jin, 2019; Wagner and Dimmeler, 2020). Extensive research is currently focused on understanding natural cellular processes that attenuate cellular senescence and remove senescent cells to prevent spreading of cellular senescence, and increasing these processes to mitigate aging-associated cardiovascular diseases via life style changes and/or longevity drugs. Loss of mTORC2 enhances autophagy/ mitophagy (Aspernig et al, 2019)
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