1. Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulation.
- Author
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Deocaris CC, Takano S, Priyandoko D, Kaul Z, Yaguchi T, Kraft DC, Yamasaki K, Kaul SC, and Wadhwa R
- Subjects
- Animals, Caenorhabditis elegans enzymology, Caenorhabditis elegans growth & development, Cell Line, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Enzyme Stability, Fibroblasts enzymology, HSP70 Heat-Shock Proteins metabolism, Humans, Longevity drug effects, Protein Denaturation, Protein Folding, Tumor Suppressor Protein p53 metabolism, Caenorhabditis elegans drug effects, Fibroblasts drug effects, Glycerol pharmacology, Hot Temperature, Molecular Chaperones metabolism, Oxidative Stress drug effects, Proteasome Endopeptidase Complex metabolism
- Abstract
Aging is associated with accumulation of toxic intracellular and extracellular protein aggregates. Cells manage "aged" proteins by mobilizing their molecular chaperones or heat shock proteins that are also considered as determinants of lifespan in diverse species. In this study, we tested whether an exogenous addition of the non-toxic chemical chaperone 'glycerol' could elicit stress and geronto-protective activities. We found that glycerol enhanced chaperoning of heat-denatured proteins. In addition to stimulating proteasome activity, glycerol led to an increased expression of the stress chaperone 'mortalin' and decreased p53 function in human cells. Glycerol-fed worms exhibited thermo-tolerance and lower level of age-associated auto-fluorescence. Through the combined stimulation of the proteasome and chaperoning activities of mortalin, in particular, glycerol treatment resulted in increased survival and fitness against oxidative- and heat-stress. These results may have significant implications in the use of glycerol as a candidate geronto-modulator in development of practical interventions for "healthy aging".
- Published
- 2008
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