Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulation

TY - JOUR

T1 - Glycerol stimulates innate chaperoning, proteasomal and stress-resistance functions: implications for geronto-manipulation

AU - Deocaris, Custer C

AU - Takano, Syuichi

AU - Priyandoko, Didik

AU - Kaul, Zeenia

AU - Yaguchi, Tomoko

AU - Kraft, David C

AU - Yamasaki, Kazuhiko

AU - Kaul, Sunil C

AU - Wadhwa, Renu

PY - 2008

Y1 - 2008

N2 - 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".

AB - 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".

U2 - 10.1007/s10522-008-9136-8

DO - 10.1007/s10522-008-9136-8

M3 - Journal article

C2 - 18344010

SN - 1389-5729

VL - 9

SP - 269

EP - 282

JO - Biogerontology

JF - Biogerontology

IS - 4

ER -