Brown-Borg H M
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, USA.
Age (Dordr). 2006 Jun;28(2):145-62. doi: 10.1007/s11357-006-9003-y. Epub 2006 Jun 8.
A positive relationship between stress resistance and longevity has been reported in a multitude of studies in organisms ranging from yeast to mice. Several mouse lines have been discovered or developed that exhibit extended longevities when compared with normal, wild-type mice of the same genetic background. These long-living lines include the Ames dwarf, Snell dwarf, growth hormone receptor knockout (Laron dwarf), IGF-1 receptor heterozygote, Little, alpha-MUPA knockout, p66(shc) knockout, FIRKO, mClk-1 heterozygote, thioredoxin transgenic, and most recently the Klotho transgenic mouse. These mice are described in terms of the reported extended lifespans and studies involving resistance to stress. In addition, caloric restriction (CR) and stress resistance are briefly addressed for comparison with genetically altered mice. Although many of the long-living mice have GH/IGF-1/insulin signaling-related alterations and enhanced stress resistance, there are some that exhibit life extension without an obvious link to this hormone pathway. Resistance to oxidative stress is by far the most common system studied in long-living mice, but there is evidence of enhancement of resistance in other systems as well. The differences in stress resistance between long-living mutant and normal mice result from complex interrelationships among pathways that appear to coordinate signals of growth and metabolism, and subsequently result in differences in lifespan.
从酵母到小鼠等多种生物体的大量研究报告了抗逆性与长寿之间的正相关关系。已经发现或培育出了几种小鼠品系，与具有相同遗传背景的正常野生型小鼠相比，它们的寿命得到了延长。这些长寿品系包括艾姆斯侏儒小鼠、斯内尔侏儒小鼠、生长激素受体基因敲除小鼠（拉伦侏儒小鼠）、胰岛素样生长因子-1受体杂合子小鼠、利特尔小鼠、α-微尿蛋白基因敲除小鼠、p66（shc）基因敲除小鼠、FIRKO小鼠、mClk-1杂合子小鼠、硫氧还蛋白转基因小鼠，以及最近的klotho转基因小鼠。这些小鼠根据所报道的延长寿命情况以及涉及抗逆性的研究进行了描述。此外，还简要讨论了热量限制（CR）和抗逆性，以便与基因改变的小鼠进行比较。尽管许多长寿小鼠具有与生长激素/胰岛素样生长因子-1/胰岛素信号相关的改变并增强了抗逆性，但也有一些小鼠表现出寿命延长，却与该激素途径没有明显联系。迄今为止，在长寿小鼠中研究最多的是抗氧化应激系统，但也有证据表明其他系统的抗逆性也有所增强。长寿突变小鼠和正常小鼠在抗逆性上的差异源于一些途径之间复杂的相互关系，这些途径似乎协调了生长和代谢信号，进而导致了寿命的差异。
