Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation

Roberto Ambra, Eugenio Mocchegiani, Robertina Giacconi, Raffaella Canali, Alessandra Rinna, Marco Malavolta, Fabio Virgili

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1475-1484
Number of pages10
JournalExperimental Gerontology
Volume39
Issue number10
DOIs
Publication statusPublished - Oct 2004

Keywords

  • Ageing
  • Centenarians
  • Heat shock protein 70
  • Zinc

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

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