Age-related Decline in Chaperone-mediated Autophagy*

By A. Cuervo, J. Dice. Journal of Biological Chemistry, 2000

660 citations recorded by the source corpus.

Intracellular protein degradation rates decrease with age in many tissues and organs. In cultured cells, chaperone-mediated autophagy, which is responsible for the selective degradation of cytosolic proteins in lysosomes, decreases with age. In this work we use lysosomes isolated from rat liver to analyze age-related changes in the levels and activities of the main components of chaperone-mediated autophagy. Lysosomes from “old” (22-month-old) rats show lower rates of chaperone-mediated autophagy, and both substrate binding to the lysosomal membrane and transport into lysosomes decline with age. A progressive age-related decrease in the levels of the lysosome-associated membrane protein type 2a that acts as a receptor for chaperone-mediated autophagy was responsible for decreased substrate binding in lysosomes from old rats as well as from late passage human fibroblasts. The cytosolic levels and activity of the 73-kDa heat-shock cognate protein required for substrate targeting to lysosomes were unchanged with age. The levels of lysosome-associated hsc73 were increased only in the oldest rats. This increase may be an attempt to compensate for reduced activity of the pathway with age.

Subfields: Cell Biology, Epidemiology, Parasitology

View Paper: https://www.semanticscholar.org/paper/1f7073091af2a0e2fa2fa26bf0ef57caa2cfb510

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Citations in the corpus

Apoptosis, autophagy, and more. (2004, neutral): “…Donati, & Gori,603 2003; Birge, 2004; Bossy-Wetzel, Barsoum, Godzik,604 Schwarzenbacher, & Lipton, 2003; Brunk & Terman,605 2002; Cho et al., 2003; Cuervo & Dice, 2000; Del606 Roso et al., 2003; Dirks & Leeuwenburgh, 2004;607 Donati et al., 2001; Ermak & Davies, 2002; Fraker608 & Lill-Elghanian,…”
Oxidative Stress and Autophagy (2006, positive): “A second front of action to promote removal of oxidized components from cells via lysosomes could originate from a better understanding of the origin and nature of lipofuscin.”
Alpha-synuclein: Pathology, mitochondrial dysfunction and neuroinflammation in Parkinson's disease. (2018, background): “CMA is a selective formof autophagy that is often up-regulated in response to cellular stress (Cuervo and Dice, 2000a; Cuervo and Dice, 2000b).”
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease (2005, background): “In addition, several risk factors for AD, including aging (Cuervo and Dice, 2000) and PS mutations (unpublished data), impair AV maturation to lysosomes.”
Ubiquitin and proteasomes: Molecular dissection of autophagy: two ubiquitin-like systems (2001, background): “Recently, Dice et al.(42) proposed this route as ‘chaperone-mediated”
The essence of senescence. (2010, background): “Early studies have demonstrated that chaperone-mediated autophagy is decreased in senescent human cells (Cuervo and Dice 2000).”
Widespread Protein Aggregation as an Inherent Part of Aging in C. elegans (2010, neutral): “with age [1,2].”