Selected contribution: Differential expression of stress-related genes with aging and hyperthermia.
Selected contribution: Differential expression of stress-related genes with aging and hyperthermia.
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DOI：
10.1152/japplphysiol.00733.2001
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发表时间：
2002-04
影响因子：
3.3
通讯作者：
Hannah J. Zhang;V. Drake;J. Morrison;L. Oberley;K. Kregel
中科院分区：
文献类型：
--
作者：
Hannah J. Zhang;V. Drake;J. Morrison;L. Oberley;K. Kregel
衰老与科普生理压力的能力下降有关。为了研究与衰老相关的应激耐受性下降的分子机制，使用含有207个应激相关基因的cDNA阵列评估了年轻和年老Fischer 344大鼠在正常温度控制条件下或在应对高温挑战时的基因表达差异。在非应激对照条件下，衰老导致参与细胞生长、死亡和信号传导的应激蛋白基因和转录物选择性上调，沿着参与抗氧化防御和药物代谢的基因下调。热应激导致两个年龄组的抗氧化剂和药物代谢类别的基因和参与DNA、RNA和蛋白质合成的转录物的广泛诱导。年老的动物在热刺激后，与细胞生长、死亡和信号传导有关的基因强烈上调，同时应激反应基因的表达沿着减弱。相比之下，年轻的动物有一个强烈的诱导应激反应基因后，高温的挑战。通过RT-PCR分析证实了所选基因表达的变化。这些研究结果表明，老化的结果在改变基因表达的热应激反应，这是减少应激蛋白的转录和氧化应激相关基因的表达增加的指示。因此，我们的研究结果支持了这样的假设，即转录变化响应生理挑战，如高温有助于在老年生物体的压力耐受性的损失。
Aging is associated with a reduced capacity to cope with physiological stress. To study the molecular mechanisms associated with the decline in stress tolerance that accompanies aging, differences in gene expression between young and old Fischer 344 rats under euthermic control conditions or in response to hyperthermic challenge were evaluated using a cDNA array containing 207 stress-related genes. In the nonstressed control condition, aging resulted in selective upregulation of stress protein genes and transcripts involved in cell growth, death, and signaling, along with a downregulation of genes involved in antioxidant defenses and drug metabolism. Heat stress resulted in a broad induction of genes in the antioxidant and drug metabolism categories and transcripts involved in DNA, RNA, and protein synthesis for both age groups. Old animals had a robust upregulation of genes involved in cell growth, death, and signaling after heat challenge, along with a blunted expression of stress-response genes. In contrast, young animals had a strong induction of stress-response genes after hyperthermic challenge. Changes in expression of selected genes were confirmed by RT-PCR analysis. These findings suggest that aging results in altered gene expression in response to heat stress that is indicative of decreased stress protein transcription and increased expression of oxidative stress-related genes. Thus our findings support the postulate that transcriptional changes in response to a physiological challenge such as hyperthermia contribute to the loss of stress tolerance in older organisms.