TY - JOUR
T1 - Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation
AU - Ambra, Roberto
AU - Mocchegiani, Eugenio
AU - Giacconi, Robertina
AU - Canali, Raffaella
AU - Rinna, Alessandra
AU - Malavolta, Marco
AU - Virgili, Fabio
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
KW - Ageing
KW - Centenarians
KW - Heat shock protein 70
KW - Zinc
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UR - http://www.scopus.com/inward/citedby.url?scp=6944252403&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2004.07.009
DO - 10.1016/j.exger.2004.07.009
M3 - Article
C2 - 15501017
AN - SCOPUS:6944252403
VL - 39
SP - 1475
EP - 1484
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
IS - 10
ER -