title: Lysosomal cell death mechanisms in aging.
abstract: Lysosomes are degradative organelles essential for cell homeostasis that regulate a variety of processes, from calcium signaling and nutrient responses to autophagic degradation of intracellular components. Lysosomal cell death is mediated by the lethal effects of cathepsins, which are released into the cytoplasm following lysosomal damage. This process of lysosomal membrane permeabilization and cathepsin release is observed in several physiopathological conditions and plays a role in tissue remodeling, the immune response to intracellular pathogens and neurodegenerative diseases. Many evidences indicate that aging strongly influences lysosomal activity by altering the physical and chemical properties of these organelles, rendering them more sensitive to stress. In this review we focus on how aging alters lysosomal function and increases cell sensitivity to lysosomal membrane permeabilization and lysosomal cell death, both in physiological conditions and age-related pathologies.
authors.affiliation: Department of Cellular and Molecular Biology, Centro de Investigaciones Biologicas, CIB-CSIC, C/Ramiro de Maeztu 9, 28040 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Gómez-Sintes
authors.affiliation: Department of Molecular Neurobiology, Centro Biologia Molecular Severo Ochoa, CSIC-UAM, C/Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Ledesma
authors.affiliation: Department of Cellular and Molecular Biology, Centro de Investigaciones Biologicas, CIB-CSIC, C/Ramiro de Maeztu 9, 28040 Madrid, Spain. Electronic address: pboya@cib.csic.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: Boya
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001343:Autophagy / Q000502:physiology; D002403:Cathepsins / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D006801:Humans; D008247:Lysosomes / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism
chemical_list: D002403:Cathepsins
keywords: Aging; Autophagy; Cathepsin; Lipids; Lysosomal cell death; Lysosomal membrane permeabilization; Lysosomes