title: Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation.
abstract: Human centenarians attract increasing interest as they hold some still undefined molecular mechanisms resulting in the achievement of exceptional old age. Recent data suggest the ability of centenarians to efficiently counter the increased cellular stress normally associated with ageing. The ubiquitous heat shock (HS) protein HSP70, expressed under the control of the heat shock transcription factor 1 (HSF-1), is recognized as one of the main chaperones associated with cell protection against stresses. In fact, HSP70 protein induction by heat, a classic well characterized cellular stress, was recently reported to be reduced in cells of most aged humans but not in centenarians. In order to investigate the molecular basis of this feature, we analyzed in vitro the time course expression of the hsp70 gene and the activation of HSF-1 in heat treated Epstein Barr virus transformed B-lymphocytes of centenarians. Our study demonstrates that lymphoblasts from centenarians maintain the transcriptional response of hsp70 gene to heat stress similar to young subjects. Such normal induction of hsp70 is associated to higher binding activity of HSF-1 that compensates an age-dependent delay in HSF-1 phosphorylation. Moreover, in vitro zinc supplementation had an age-dependent effect on hsp70 expression, indicating a role for this nutritionally important molecule and suggesting its involvement in cellular stress responses.
authors.affiliation: National Institute for Food and Nutrition Research (INRAN), Free radicals Res Group, 546 via Ardeatina, I00178 Rome, Italy. ambra@inran.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Ambra
authors.forename: Eugenio
authors.initials: E
authors.lastname: Mocchegiani
authors.forename: Robertina
authors.initials: R
authors.lastname: Giacconi
authors.forename: Raffaella
authors.initials: R
authors.lastname: Canali
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rinna
authors.forename: Marco
authors.initials: M
authors.lastname: Malavolta
authors.forename: Fabio
authors.initials: F
authors.lastname: Virgili
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D002472:Cell Transformation, Viral; D004268:DNA-Binding Proteins / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000097:blood* / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D014157:Transcription Factors / Q000235:genetics; D019287:Zinc Sulfate / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D019287:Zinc Sulfate