Lucanic Mark, Graham Jill, Scott Gary, Bhaumik Dipa, Benz Christopher C, Hubbard Alan, Lithgow Gordon J, Melov Simon
Buck Institute for Research on Aging, 8001 Redwood Boulevard, Novato, CA 94945, USA.
Aging (Albany NY). 2013 Jun;5(6):394-411. doi: 10.18632/aging.100564.
Non-coding small RNAs of the micro-RNA class (miRNA) are conserved regulators of gene function with a broad impact on biological processes. We screened miRNA levels for age-related changes in individual worms and investigated their influence on the lifespan of the nematode C. elegans. We measured the abundance of 69 miRNAs expressed in individual animals at different ages with over thirty five thousand discrete quantitative nano-fluidic polymerase chain reactions. We found that miRNA abundance was highly variable between individual worms raised under identical conditions and that expression variability generally increased with age. To identify expression differences associated with either reproductive or somatic tissues, we analyzed wild type and mutants that lacked germlines. miRNAs from the mir-35-41 cluster increased in abundance with age in wild type animals, but were nearly absent from mutants lacking a germline, suggesting their age-related increase originates from the germline. Most miRNAs with age-dependent levels did not have a major effect on lifespan, as corresponding deletion mutants exhibited wild-type lifespans. The major exception to this was mir-71, which increased in abundance with age and was required for normal longevity. Our genetic characterization indicates that mir-71 acts at least partly in parallel to insulin/IGF like signals to influence lifespan.
微小RNA(miRNA)类的非编码小RNA是基因功能的保守调节因子,对生物过程具有广泛影响。我们筛选了单个线虫中与年龄相关的miRNA水平变化,并研究了它们对线虫秀丽隐杆线虫寿命的影响。我们通过超过三万五千次离散定量纳米流体聚合酶链反应,测量了不同年龄的单个动物中表达的69种miRNA的丰度。我们发现,在相同条件下饲养的单个线虫之间,miRNA丰度高度可变,并且表达变异性通常随年龄增加。为了确定与生殖或体细胞组织相关的表达差异,我们分析了野生型和缺乏生殖系的突变体。来自mir-35-41簇的miRNA在野生型动物中随年龄增加而丰度增加,但在缺乏生殖系的突变体中几乎不存在,这表明它们与年龄相关的增加起源于生殖系。大多数具有年龄依赖性水平的miRNA对寿命没有重大影响,因为相应的缺失突变体表现出野生型寿命。主要例外是mir-71,其丰度随年龄增加,是正常长寿所必需的。我们的遗传特征表明,mir-71至少部分地与胰岛素/IGF样信号平行作用以影响寿命。