A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.

A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility.
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DOI:
10.1093/genetics/118.1.75
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发表时间:
2002-09
期刊:
影响因子:
3.3
通讯作者:
D. Friedman;T. Johnson
D. Friedman;T. Johnson
中科院分区:
生物学2区
文献类型:
--
作者:
D. Friedman;T. Johnson

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age-1(hx546)是秀丽隐杆线虫的一种隐性突变等位基因,在20度时可使平均寿命增加40%,最大寿命增加60%;25度龄1(hx546)平均寿命增加65%(25.3天比15.0天),最大寿命增加110%(46.2天比22.0天,野生型雌雄同体)。变异的雄性也表现出更长的寿命。与年龄1+等位基因相比,年龄1(hx546)在20度时与雌雄同体自我生育能力降低75%相关。使用两种新的策略来跟踪年龄-1的分离,我们提出证据表明,更长的寿命源于单个基因的突变,该突变增加了在所有实际年龄的生存概率。长寿命和低生育表型共分离,并与连锁群II上的一个位点fer-15紧密相连。年龄1(hx546)不影响幼虫蜕皮的时间、胚胎发育的长度、食物摄取、运动或任何方式的行为。虽然年龄1(hx546)降低了雌雄同体的自我生育能力,但它对生殖期的长度没有显著影响,因为预期寿命的增加是由于生殖后寿命的增加。就我们所知,这个1岁的突变体是唯一一个具有良好特征的基因位点的实例,其中突变形式导致寿命延长。age-1在延长寿命方面的作用很可能不是由于消除了一种程序化的衰老功能,而是由于雌雄同体自我生育能力的减少或其他一些未知的代谢或生理改变。
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.