Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.

Abstract

Lysosomes are degradation centers and signaling hubs that in cells and play important roles in cellular homeostasis, development, and aging. Growing evidence has also implicated the role of lysosome-related mechanisms in the aging process. Meanwhile, the potential impact of lysosomal dysfunction on the production of inflammatory molecules, cellular metabolic status, and mitochondrial function is becoming increasingly significant. In this review, we provide a comprehensive overview of the physiological roles of lysosomes and their association with aging. At the cellular level, lysosomal dysfunction and cellular senescence show strong correlations. Herein, we elucidated the precise mechanisms by which lysosomal dysfunction contributes to various cellular physiological processes, as well as its potential implications in age-related hallmarks. More importantly, we discuss how lysosomal homeostasis is disrupted in several age-related diseases, including atherosclerosis, heart diseases, cancer, neurodegenerative diseases, metabolic disorders, and motor system diseases. Thus, a deeper understanding of lysosomal function may provide fundamental insights into human physiology and age-related diseases. Furthermore, these discoveries emphasize the role of the lysosome in the development of novel therapeutic strategies.