A look at MERCs as UPRmt regulatory hubs in age-associated heart diseases.

Life expectancy has increased considerably worldwide; therefore, aging is considered to be a causal risk factor for various diseases, such as cardiovascular diseases, which weaken human beings throughout their lives. Mitochondria have been described as central elements in the aging process for many years; in this sense, cells require close interorganellar communication to maintain homeostasis, especially with mitochondria. Nevertheless, this has serious limitations with respect to organism age. The mitochondrial unfolded protein response (UPRmt) is activated under stress conditions to maintain mitochondrial homeostasis during aging and disease. In the UPRmt signaling pathway, several signaling cascades are activated through rapid signal transmission from the mitochondria to the nucleus, providing transcriptional responses that help prevent the accumulation of damaged proteins in the organism. In this review, we address the role of mitochondria in terms of function and morphology in the aged heart and subsequently describe the influence of UPRmt on the progression of cardiac diseases such as heart failure, acute myocardial infarction, and dilated cardiomyopathy. Finally, based on recently published literature, we provide a brief and current overview of mitochondria-endoplasmic reticulum contact sites (MERCs) as possible modulators of UPRmt in aging to reinforce our understanding of possible protective signals in old organisms.