Aging-driven organelle miscommunication in the failing heart

Abstract

Cardiovascular diseases are the leading cause of death in older adults worldwide, with heart failure (HF) representing one of their most serious end stages. Aging is a non-modifiable risk factor that drives a series of structural and functional changes in the heart, both at the macro and subcellular levels. This review article analyzes how intracellular organelle dysfunction and the loss of coordination between them, a process termed “interorganelle miscommunication,” contribute to the progression of HF in the context of aging. We review experimental and clinical studies on the function of mitochondria, sarcoplasmic reticulum, lysosomes, lipid droplets, and the nucleus in aging cardiomyocytes. Particular emphasis is placed on how altered interactions between these organelles affect key processes such as ATP production, calcium handling, autophagy, epigenetic regulation, and oxidative stress control. We also discuss the impact of chronic low-grade inflammation (“inflammaging”) and cellular senescence as aggravating factors in cardiac functional decline. Collectively, the evidence indicates that dysregulation of interorganelle communication not only accelerates cardiac aging but also represents a central pathogenetic mechanism in HF. In this context, the concept of a “dysfunctional interorganellar network” may serve as a new hallmark of subcellular aging and an emerging therapeutic target for preventing or delaying age-related HF.

Keywords

Heart failure / aging / organelles / organelle communication

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