Protein homeostasis and molecular chaperones in aging
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Molecular chaperones are ubiquitous, highly conserved proteins responsible for the maintenance of protein folding homeostasis in cells. Environmental stress causes proteotoxic damage, which triggers chaperone induction and the subsequent reparation of cellular damage by chaperones, including disposing irreparable protein ensembles. We summarize the current view of protein damage, turnover, the stress response and chaperone function in aging, and review novel data showing that accumulation of misfolded proteins outcompete and overload the limited resources of the protein folding, maintenance and turnover system, compromising general protein homeastasis and cellular function. Possible involvement of chaperones and proteolysis in immunosenescence is highlighted. Defects in zinc metabolism are also addressed in relation to aging and changes in chaperone levels.
KeywordsHeat shock protein Stress protein Chaperones-chaperone overload Aging Neurodegenerative diseases Protein folding Protein damage Zinc Metallothionein Immune response
94 kDa glucose regulated protein
Heat shock transcription factor
Heat shock protein, the number thereafter denotes molecular weight
Reactive oxygen species
Work in the authors’ laboratory was supported by research grants from the EU 6th Framework program (FP6506850, FP6518230), Hungarian Science Foundation (OTKA-F47281) and from the Hungarian National Research Initiative (1A/056/2004 and KKK-0015/3.0). C.S. is a Bolyai research Scholar of the Hungarian Academy of Sciences. The authors apologize for not citing a number of excellent publications due to space limitations.
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