Lysosomes in senescence and aging.

Autor: Tan JX; Aging Institute, University of Pittsburgh School of Medicine/University of Pittsburgh Medical Center, Pittsburgh, PA, USA.; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Finkel T; Aging Institute, University of Pittsburgh School of Medicine/University of Pittsburgh Medical Center, Pittsburgh, PA, USA.; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Jazyk: angličtina
Zdroj: EMBO reports [EMBO Rep] 2023 Nov 06; Vol. 24 (11), pp. e57265. Date of Electronic Publication: 2023 Oct 09.
DOI: 10.15252/embr.202357265
Abstrakt: 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.
(© 2023 The Authors.)
Databáze: MEDLINE