The Impact of Autophagy on Cardiovascular Senescence and Diseases

Abstract

SummaryThe risk of cardiovascular disease increases with age, causing chronic disability, morbidity, and mortality in the elderly. Cardiovascular aging and disease are characterized by heart failure, cardiac ischemia-reperfusion injury, cardiomyopathy, hypertension, arterial stiffness, and atherosclerosis. As a cell ages, damaged organelles and abnormal proteins accumulate. A system for removing these cytoplasmic substrates is essential for maintaining homeostasis. Autophagy assists tissue homeostasis by forming a pathway by which these substances are degraded. Growing evidence suggests that autophagy plays a role in age-related and disease states of the cardiovascular system, and it may even be effective in preventing or treating cardiovascular disease. On the other hand, overexpression of autophagy in the heart and arteries can produce detrimental effects. We summarize the current understanding of the close relationship between autophagy and cardiovascular senescence.(Int Heart J 2017; 58: 666-673) Key words: Cardiovascular disease, Aging, Heart failure, Atherosclerosis T he human life span has significantly increased over recent decades and is expected to increase even further. Consequently, the prevalence of agerelated cardiovascular disease is also increasing. 1) Many risk factors for cardiovascular disease, such as hypertension, diabetes mellitus, dyslipidemia, and metabolic syndrome, emerge with age, and cardiovascular disease is the leading cause of chronic disability, morbidity, and mortality among the elderly. 2,3)The aging heart is associated with increases in left ventricular wall thickness, stiffness, and chamber size, as well as changes in the diastolic filling pattern, which can lead to cardiac dysfunction. 4,5) Age-related loss of vascular elasticity and stiffness increases cardiac after-load in the elderly. [6][7][8] As the body ages, damaged organelles and abnormal proteins accumulate, disrupting cellular homeostasis.9-11) A system for eliminating damaged organelles, proteins, and intracellular pathogens is critical for maintaining cellular homeostasis as the body ages. In recent years, it has become evident that autophagy plays a pivotal role in this regard. 12,13) In particular, autophagy functions as part of a pathway that delivers cytoplasmic substrates to lysosomes for subsequent degradation and removal. Autophagy modulates homeostasis and the body's response to stress, including energy deprivation in the heart, and altered autophagy is related to cardiovascular aging and disease.14-18) Because autophagy attenuates with age, interventions that increase autophagy may in turn reduce agerelated cardiovascular disease, prolonging the lifespan. 19-21)On the other hand, overexpression of autophagy in the heart can induce atrophy of cardiomyocytes, increasing the risk of ischemia-reperfusion injury. 22,23) This review summarizes our current understanding of the close relationship between autophagy and cardiovascular senescence. Three Types of AutophagyAutophagy is classified into 3 subtypes: macr...

Metformin mediates cardioprotection against aging‐induced ischemic necroptosis

“…As a physiological process that effectively prevents the accumulation of abnormal proteins and organelles, autophagy is crucial for maintaining cell self‐renewal and energy homeostasis (Sciarretta, Maejima, Zablocki, & Sadoshima, ). Autophagy preserves cardiac structure and function under baseline conditions and is activated during stress (Sasaki, Ikeda, Iwabayashi, Akasaki, & Ohishi, ), limiting damage under most conditions (Sciarretta et al, ). Functional autophagy reduces injury and preserves cardiac function during ischemia (Godar et al, ; Sciarretta, Yee, Shenoy, Nagarajan, & Sadoshima, ).…”

Changes in Autophagy Levels in Rat Myocardium During Exercise Preconditioning-Initiated Cardioprotective Effects

“…12) Autophagy is maintained at low levels under normal conditions, but this process is altered by several pathological or physiological conditions, such as starvation, endoplasmic reticulum stress, oxidative stress, aging, and disease pathogenesis. [13][14][15][16][17] Previous studies reported autophagy levels were inhibited in the ischemic myocardium in both in vitro and in vivo models of heart I/R injury. 18,19) Enhanced autophagic flux functions as a protective countermeasure against I/R injury in cardiac myocytes.…”

Rhynchophylline Attenuates Senescence of Endothelial Progenitor Cells by Enhancing Autophagy

“…Autophagy plays a crucial role in prolonging longevity, and it has been proposed that autophagy is bound up with organ aging (Sasaki et al, 2017) and cell senescence (Levine and Kroemer, 2008). Damaged organelles and abnormal proteins accumulate continuously as cells age, while autophagy maintains tissue homeostasis by degrading these substances.…”