Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA.
Exp Gerontol. 2011 May;46(5):355-62. doi: 10.1016/j.exger.2010.09.002. Epub 2010 Sep 16.
Since their discovery in Drosophila, the heat shock proteins (Hsps) have been shown to regulate both stress resistance and life-span. Aging is characterized by increased oxidative stress and the accumulation of abnormal (malfolded) proteins, and these stresses induce Hsp gene expression through the transcription factor HSF. In addition, a subset of Hsps is induced by oxidative stress through the JNK signaling pathway and the transcription factor Foxo. The Hsps counteract the toxicity of abnormal proteins by facilitating protein refolding and turnover, and through other mechanisms including inhibition of apoptosis. The Hsps are up-regulated in tissue-specific patterns during aging, and their expression correlates with, and sometimes predicts, life span, making them ideal biomarkers of aging. The tools available for experimentally manipulating gene function and assaying healthspan in Drosophila provides an unparalleled opportunity to further study the role of Hsps in aging.
自在果蝇中发现热休克蛋白(Hsps)以来,它们已被证明可以调节应激抗性和寿命。衰老的特征是氧化应激增加和异常(错误折叠)蛋白质的积累,这些应激通过转录因子 HSF 诱导 Hsp 基因表达。此外,一组 Hsps 通过 JNK 信号通路和转录因子 Foxo 被氧化应激诱导。Hsps 通过促进蛋白质重折叠和周转以及通过包括抑制细胞凋亡在内的其他机制来抵消异常蛋白质的毒性。Hsps 在衰老过程中以组织特异性模式上调,其表达与寿命相关,有时甚至可以预测寿命,因此它们是衰老的理想生物标志物。在果蝇中实验性操纵基因功能和测定健康寿命的可用工具为进一步研究 Hsps 在衰老中的作用提供了无与伦比的机会。