Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulation.
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".
Deocaris
Custer C
CC
National Institute of Advanced Industrial Science & Technology (AIST), Central 4, 1-1-1 Higashi, Tsukuba, 305 8562, Japan. custerd@biochem.taiiku.tsukuba.ac.jp
Takano
Syuichi
S
Priyandoko
Didik
D
Kaul
Zeenia
Z
Yaguchi
Tomoko
T
Kraft
David C
DC
Yamasaki
Kazuhiko
K
Kaul
Sunil C
SC
Wadhwa
Renu
R
D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004795:Enzyme Stability; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D005990:Glycerol / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008136:Longevity / Q000187:drug effects; D018832:Molecular Chaperones / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011489:Protein Denaturation; D017510:Protein Folding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C080352:mortalin; D046988:Proteasome Endopeptidase Complex; D005990:Glycerol