How do intracellular proteolytic systems change with age?

Ana Maria Cuervo, J. F. Dice

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

One of the common features of cells from senescent tissues is the accumulation of abnormal proteins. Several hypotheses have been proposed to explain the origin of those abnormal proteins. A defect in proteolytic systems usually responsible for the elimination of altered proteins from the cells could clearly contribute to such accumulation. Here we describe the effect of age on the major proteolytic systems within cells: the ubiquitin-proteasome pathway, the calcium-activated calpain pathways, and multiple lysosomal pathways. Our group has contributed to the characterization of a selective pathway of degradation of cytosolic proteins in lysosomes that is activated under conditions of nutrient deprivation. In this lysosomal pathway of proteolysis proteins are transported through the lysosomal membrane assisted by cytosolic and lysosomal molecular chaperones and a receptor protein in the lysosomal membrane. The activity of this pathway significantly decreases with age, and this decrease might account for the cytosolic accumulation of aberrant substrate proteins in senescent cells. The cellular consequences of the decline of this lysosomal pathway together with possible methods to restore the reduced function are also addressed in this review.

Original languageEnglish (US)
JournalFrontiers in Bioscience
Volume3
StatePublished - 1998
Externally publishedYes

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Proteins
Proteolysis
Lysosome-Associated Membrane Glycoproteins
Molecular Chaperones
Calpain
Proteasome Endopeptidase Complex
Ubiquitin
Lysosomes
Membranes
Calcium
Nutrients
Food
Tissue
Degradation
Defects
Substrates

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How do intracellular proteolytic systems change with age? / Cuervo, Ana Maria; Dice, J. F.

In: Frontiers in Bioscience, Vol. 3, 1998.

Research output: Contribution to journalArticle

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