Endoplasmic reticulum stress, calcium homeostasis, and the aging heart

Aging is a process characterized by the progressive decline in physiological function and increased susceptibility to disease. Many cellular functions, including unfolded protein responses (UPR, an endoplasmic reticulum stress coping mechanism), Ca²⁺ signaling, cellular signaling, and inflammatory responses are affected by aging. These significantly impact Ca²⁺ handling by cardiac cells and the architecture of cardiomyocytes, leading to impaired contractility, and increased risk of arrhythmias. Cellular Ca²⁺ homeostasis and the UPR are interdependent, therefore, understanding and influencing these key cellular pathways should provide new therapeutic strategies for managing age-related cardiac diseases. Modulating Ca²⁺ handling and cellular stress pathways presents distinctive approaches to preventing molecular alterations linked to aging, while providing opportunities to reduce molecular damage and promote the effectiveness of cellular repair processes.