Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation
Characterization of the hsp70 response in lymphoblasts from aged and centenarian subjects and differential effects of in vitro zinc supplementation
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DOI：
10.1016/j.exger.2004.07.009
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发表时间：
2004-10-01
影响因子：
3.9
通讯作者：
Virgili, F
中科院分区：
文献类型：
--
作者：
Ambra, R;Mocchegiani, E;Virgili, F
人类百岁老人吸引了越来越多的兴趣，因为他们持有一些尚未确定的分子机制，导致实现特殊的老年。最近的数据表明，百岁老人有能力有效地对抗通常与衰老有关的细胞压力增加。普遍存在的热休克（HS）蛋白HSP 70在热休克转录因子1（HSF-1）的控制下表达，被认为是与细胞抗应激相关的主要分子伴侣之一。事实上，热诱导的HSP 70蛋白是一种典型的细胞应激反应，最近有报道称，在大多数老年人的细胞中，HSP 70蛋白的诱导作用会减少，但在百岁老人中则不会。为了研究这一特征的分子基础，我们在体外分析了热处理的EB巴尔病毒转化的百岁老人B淋巴细胞中热休克蛋白70基因的时程表达和HSF-1的活化。我们的研究表明，百岁老人的淋巴母细胞保持热应激的热休克蛋白70基因的转录反应类似于年轻人。这种正常的hsp 70诱导与HSF-1更高的结合活性相关，其补偿了HSF-1磷酸化的年龄依赖性延迟。此外，在体外补锌对热休克蛋白70的表达有年龄依赖性的影响，表明这种营养重要的分子的作用，并建议其参与细胞应激反应。(C)2004年爱思唯尔公司All rights reserved.
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. (C) 2004 Elsevier Inc. All rights reserved.