Abstract
Ageing populations present substantial healthcare challenges, with cardiovascular disease (CVD) remaining the predominant cause of morbidity and mortality globally. Cardiac ageing is characterised by progressive cellular and molecular changes, contributing to structural and functional decline and predisposition to CVD. Component proteins (nucleoporins) of the Nuclear Pore Complex (NPC) and the nuclear lamina are both crucial for nuclear integrity and chromatin organisation, and have appeared as key players in cellular homeostasis of post-mitotic cells. Age-related changes in NPC composition and turnover, particularly in non-dividing cells, compromise nucleocytoplasmic compartmentalisation and drive genomic instability, cell death, and senescence. Emerging evidence implicates aberrant NPC components in the core hallmarks of cardiac ageing and in distinct heart diseases. Additionally, the nuclear lamina’s susceptibility to damage and its interactions with NPCs might exacerbate these effects. This review presents evidence linking NPC and nuclear lamina dysfunction to features of the ageing heart and suggests that age-related NPC alterations are potential drivers of cardiomyocyte and cardiac decline with age
•Cardiovascular ageing contributes significantly to morbidity and mortality.•Loss of cardiomyocyte homeostasis is a significant contributor to declining cardiac function with age.•Many nuclear proteins are long-lived and are turned over slowly or not at all in post-mitotic cells.•Emergent age-related defects in nuclear proteins lead to loss of cellular homeostasis.•Nuclear Pore Complex and nuclear lamina dysfunction is linked to features of aged and diseased hearts.