Abstract
Aging is a physiological process defined by decreased cellular and tissue functions. Reduced capacity of protein degradation is one of the important hallmarks of aging that may lead to misfolded protein accumulation and progressive loss of function in organ systems. Recognition of unfolded/misfolded protein aggregates via endoplasmic reticulum (ER) stress sensors activates an adaptive mechanism, the unfolded protein response (UPR). The initial step of UPR is defined by chaperone enhancement, ribosomal translation suppression, and misfolded protein degradation, while prolonged ER stress triggers apoptosis. MicroRNAs (miRNAs) are non-coding RNAs affecting various signaling pathways through degradation or translational inhibition of targeted mRNAs. Therefore, UPR and miRNA impairment in aging and age-related diseases is implicated in various studies. This review will highlight the recent insights in ER stress–miRNAs alterations during aging and age-related diseases, including metabolic, cardiovascular, and neurodegenerative diseases and several cancers.
Highlights
Aging is a process that results in decreased body homeostasis and increased risk of disease or death (Ito and Barnes, 2009)
Many studies have determined that endoplasmic reticulum (ER) chaperones (PDI, glucose-regulated protein 78 (GRP78), and glucose-regulated protein 94 (GRP94)) and unfolded protein response (UPR) signaling are decreased in aging cells (Naidoo et al, 2008)
Numerous studies greatly expanded our understanding of the effect of miRNAs during aging. These findings indicate miRNA alterations, additional studies are needed to inspire the use of miRNAs therapeutically
Summary
Aging is a process that results in decreased body homeostasis and increased risk of disease or death (Ito and Barnes, 2009). Nine hallmarks in aging have been described as follows: 1) telomere attrition, 2) epigenetic alterations, 3) genomic instability, 4) mitochondrial dysfunction, 5) deregulated nutrient sensing, 6) cellular senescence, 7) stem cell exhaustion, 8) altered intercellular communication, and 9) loss of proteostasis (Lopez-Otin et al, 2013). Metabolic disorders, including obesity, cardiovascular diseases (CVDs), and neurodegenerative disorders, have been described as other hallmarks in the aging process (Spinelli et al, 2020)
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