Protein homeostasis in the aged and diseased heart

Abstract

Protein homeostasis, the balance between protein synthesis and degradation, requires the clearance of misfolded and aggregated proteins and is therefore considered to be an essential aspect of establishing a physiologically effective proteome. Aging alters this balance, termed "proteostasis", resulting in the progressive accumulation of misfolded and aggregated proteins. Defective proteostasis leads to the functional deterioration of diverse regulatory processes during aging and is implicated in the etiology of multiple pathological conditions underlying a variety of neurodegenerative diseases and in age-dependent cardiovascular disease. Detergent-insoluble protein aggregates have been reported by us in both aged and hypertensive hearts. The protein constituents were found to overlap with protein aggregates seen in neurodegenerative diseases such as Alzheimer's disease. Therefore, targeting these protein components of aggregates may be a promising therapeutic strategy for cardiovascular pathologies associated with aging, ischemia, and/or hypertension.

Ischemic heart disease and cardiac arrhythmia are associated with increased cardiac aging

“…Hypertension is a common risk factors for aging and IHD due to the increased risk of atherosclerosis, LV afterload, and microvascular remodelling [1]. Recent evidence suggests shared protein aggregation pathways in aging, hypertension, and MI, supporting our ndings that IHD and VRFs hasten cardiac aging [29]. A rising waist-to-hip ratio, indicative of visceral obesity, was found to accelerate cardiac aging most substantially in IHD.…”

Molecular mechanisms underlying sarcopenia in heart failure

“…Cardiomyocytes are terminally differentiated, so the removal of protein aggregates and damaged protein is critical to avoiding cell death and cardiac fibrosis. Alterations in cardiac proteostasis have been demonstrated within several cardiac disease models, including ischemia [ 121 ] , arrhythmia [ 122 ] , and heart failure [ 123 ] , as well as in the aging heart [ 124 ] . Alterations in muscle proteostasis are critical changes in the development of sarcopenia as well [ 125 ] .…”