Cypser James R, Tedesco Pat, Johnson Thomas E
University of Colorado, Institute for Behavioral Genetics, Box 447 Boulder, CO 80309, Fedex, 1480 30th St., Boulder, CO 80303, USA.
Exp Gerontol. 2006 Oct;41(10):935-9. doi: 10.1016/j.exger.2006.09.004. Epub 2006 Oct 24.
Hormesis has emerged as an important manipulation for the study of aging. Although hormesis is manifested in manifold combinations of stress and model organism, the mechanisms of hormesis are only partly understood. The increased stress resistance and extended survival caused by hormesis can be manipulated to further our understanding of the roles of intrinsic and induced stress resistance in aging. Genes of the dauer/insulin/insulin-like signaling (IIS) pathway have well-established roles in aging in Caenorhabditis elegans. Here, we discuss the role of some of those genes in the induced stress resistance and induced life extension attributable to hormesis. Mutations in three genes (daf-16, daf-18, and daf-12) block hormetically induced life extension. However, of these three, only daf-18 appears to be required for a full induction of thermotolerance induced by hormesis, illustrating possible separation of the genetic requirements for stress resistance and life extension. Mutations in three other genes of this pathway (daf-3, daf-5, and age-1) do not block induced life extension or induced thermotolerance; daf-5 mutants may be unusually sensitive to hormetic conditions.
毒物兴奋效应已成为衰老研究中的一项重要操作手段。尽管毒物兴奋效应在压力与模式生物的多种组合中均有体现，但人们对其机制的理解仍不全面。毒物兴奋效应所引发的应激抗性增强和生存期延长，可被用于深化我们对内在和诱导性应激抗性在衰老过程中作用的理解。 dauer/胰岛素/胰岛素样信号传导（IIS）通路的基因在秀丽隐杆线虫的衰老过程中具有已明确的作用。在此，我们探讨其中一些基因在毒物兴奋效应所致的诱导性应激抗性和诱导性寿命延长中的作用。三个基因（daf-16、daf-18和daf-12）的突变会阻断毒物兴奋效应诱导的寿命延长。然而，在这三个基因中，似乎只有daf-18是毒物兴奋效应诱导的热耐受性完全诱导所必需的，这表明应激抗性和寿命延长的遗传需求可能存在分离。该通路的其他三个基因（daf-3、daf-5和age-1）的突变不会阻断诱导性寿命延长或诱导性热耐受性；daf-5突变体可能对毒物兴奋效应条件异常敏感。
