Maintenance and Decline of Neuronal Lysosomal Function in Aging

Lysosomes are central effectors of cellular maintenance, integrating the degradation of damaged organelles and protein aggregates with macromolecule recycling and metabolic signaling. In neurons, lysosomes are particularly crucial due to the cells' long lifespan, polarized architecture, and high metabolic demands. Proper regulation of lysosomal function is essential to sustain proteostasis, membrane turnover, and synaptic integrity. Although lysosomal dysfunction has been extensively studied in neurodegenerative diseases, far less is known about how lysosomal capacity and function are maintained-or fail to be maintained-with age in non-diseased neurons. In this review, we summarize current understanding of neuronal lysosomal dynamics, discuss methodological challenges in assessing lysosomal capacity and function, and highlight recent advances that reveal age-associated decline in neuronal lysosomal competence.