Lysosomes in senescence and aging

Dysfunction of lysosomes, the primary hydrolytic organelles in animal cells, is frequently associated with aging and age-related diseases. At the cellular level, lysosomal dysfunction is strongly linked to cellular senescence or the induction of cell death pathways. However, the precise mechanisms by which lysosomal dysfunction participates in these various cellular or organismal phenotypes have remained elusive. The ability of lysosomes to degrade diverse macromolecules including damaged proteins and organelles puts lysosomes at the center of multiple cellular stress responses. Lysosomal activity is tightly regulated by many coordinated cellular processes including pathways that function inside and outside of the organelle. Here, we collectively classify these coordinated pathways as the lysosomal processing and adaptation system (LYPAS). We review evidence that the LYPAS is upregulated by diverse cellular stresses, its adaptability regulates senescence and cell death decisions, and it can form the basis for therapeutic manipulation for a wide range of age-related diseases and potentially for aging itself. Lysosomes are cellular quality control organelles whose dysfunction is associated with many human diseases. In this review, the authors introduce the concept of the lysosomal processing and adaptation system (LYPAS), discuss how the system responds to diverse cellular stresses, and propose that expanding the capacity of LYPAS or preventing its exhaustion suppresses senescence and cell death.image

Automated summary

Dysfunction of lysosomes is associated with aging and age-related diseases, and the regulation of the lysosomal processing and adaptation system (LYPAS) may have therapeutic implications for such diseases.