Organelle dysfunction and its contribution to metabolic impairments in aging and age-related diseases

Abstract

Aging is a major risk factor for most diseases. Pathways regulating metabolism, including nutrient sensing, energy production, and synthesis and degradation of macromolecules, have been identified as key regulators of organismal lifespan and implicated in several late-onset diseases, such as most neurodegenerative disorders. In this review, we focus on emerging evidence that links the remodeling of key organelles, namely mitochondria and lysosomes, to metabolic alterations that manifest during the aging process. We highlight data demonstrating a reciprocal interaction between organelle (dys)-function and protein homeostasis in aging. We also discuss examples of cell-type-specific metabolic alterations that can influence organ function locally and whole organism aging via inter-tissue communication. Finally, we propose how emerging methods could enable to characterize in vivo the impact of aging on organelle composition and function.