Friedman D B, Johnson T E
Department of Molecular Biology and Biochemistry, University of California, Irvine, 92717, USA.
Genetics. 1988 Jan;118(1):75-86. doi: 10.1093/genetics/118.1.75.
age-1(hx546) is a recessive mutant allele in Caenorhabditis elegans that results in an increase in mean life span averaging 40% and in maximal life span averaging 60% at 20 degrees; at 25 degrees age-1(hx546) averages a 65% increase in mean life span (25.3 days vs. 15.0 days) and a 110% increase in maximum life span (46.2 days vs. 22.0 days for wild-type hermaphrodites). Mutant males also show extended life spans. age-1(hx546) is associated with a 75% decrease in hermaphrodite self-fertility as compared to the age-1+ allele at 20 degrees. Using two novel strategies for following the segregation of age-1, we present evidence that longer life results from a mutation in a single gene that increases the probability of survival at all chronological ages. The long-life and reduced-fertility phenotypes cosegregate and are tightly linked to fer-15, a locus on linkage group II. age-1(hx546) does not affect the timing of larval molts, the length of embryogenesis, food uptake, movement, or behavior in any way tested. Although age-1(hx546) lowers hermaphrodite self-fertility, it does not markedly affect the length of the reproductive period with all the increase in life expectancy due to an increase in the length of postreproductive life. In so far as we are aware, this mutant in age-1 is the only instance of a well-characterized genetic locus in which the mutant form results in lengthened fife. It is likely that the action of age-1 in lengthening life results not from eliminating a programmed aging function but rather from reduced hermaphrodite self-fertility or from some other unknown metabolic or physiologic alteration.
age-1(hx546)是秀丽隐杆线虫中的一个隐性突变等位基因,在20摄氏度时,它使平均寿命平均增加40%,最大寿命平均增加60%;在25摄氏度时,age-1(hx546)平均使平均寿命增加65%(25.3天对15.0天),最大寿命增加110%(46.2天对野生型雌雄同体的22.0天)。突变雄性的寿命也延长。与20摄氏度时的age-1+等位基因相比,age-1(hx546)使雌雄同体的自体受精能力降低75%。通过两种追踪age-1分离的新策略,我们提供证据表明,更长的寿命源于单个基因突变,该突变增加了所有实足年龄的存活概率。长寿和低生育力表型共分离,并且与fer-15紧密连锁,fer-15是连锁群II上的一个位点。age-1(hx546)在任何测试方式下都不影响幼虫蜕皮时间、胚胎发生长度、食物摄取、运动或行为。虽然age-1(hx546)降低了雌雄同体的自体受精能力,但它并没有显著影响生殖期的长度,寿命的增加完全是由于生殖后期长度的增加。就我们所知,age-1中的这种突变是一个特征明确的基因位点的唯一实例,其中突变形式导致寿命延长。age-1延长寿命的作用可能不是由于消除了程序性衰老功能,而是由于雌雄同体自体受精能力降低或其他一些未知的代谢或生理改变。