Lifelong leukocyte telomere dynamics and survival in a free-living mammal.
Lifelong leukocyte telomere dynamics and survival in a free-living mammal.
复制标题
终生的白细胞端粒动力学和自由哺乳动物中的生存。
DOI：
10.1111/acel.12417
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发表时间：
2016-02
期刊：
影响因子：
7.8
通讯作者：
Nussey DH
中科院分区：
文献类型：
--
作者：
Fairlie J;Holland R;Pilkington JG;Pemberton JM;Harrington L;Nussey DH
端粒在细胞水平上维持基因组完整性方面起着重要作用，白细胞端粒平均长度（LTL）已被提出作为生物体衰老的生物标志物。然而，缺乏在个人整个生命过程中跟踪LTL的研究。在这里，我们研究了终身模式的变化，在LTL之间的四个出生队列的女性Soay羊（绵羊），纵向监测和采样从出生到死亡。在出生后的前4个月，存在个体内LTL损失，与人类和灵长类动物文献中的结果一致，但几乎没有证据表明LTL损失与年龄相关。总的来说，我们只观察到几年来和整个生命周期中LTL个体一致性的微弱证据：个体内变异相当大，出生队列的端粒动力学差异显著。尽管在个体的一生中LTL变异水平很高，但LTL和寿命之间仍然存在显着的关联。对纵向数据集的详细分析表明，这种关联是由在生命的前2年具有较长LTL的个体的生存率提高所驱动的。没有证据表明LTL可以预测成年后期的生存。我们的数据提供了来自哺乳动物的第一个证据，即LTL可以预测自然条件下的死亡率和寿命，并且还突出了LTL在经历复杂和高度可变环境的个体的生命周期内的潜在动态性质。
Telomeres play a fundamental role in the maintenance of genomic integrity at a cellular level, and average leukocyte telomere length (LTL) has been proposed as a biomarker of organismal aging. However, studies tracking LTL across the entire life course of individuals are lacking. Here, we examined lifelong patterns of variation in LTL among four birth cohorts of female Soay sheep (Ovis aries) that were longitudinally monitored and sampled from birth to death. Over the first 4 months of life, there was within‐individual loss of LTL, consistent with findings in the human and primate literature, but there was little evidence of consistent LTL loss associated with age after this point. Overall, we observed only weak evidence of individual consistency in LTL across years and over the entire lifespan: Within‐individual variation was considerable, and birth cohorts differed markedly in their telomere dynamics. Despite the high levels of LTL variation within the lifetimes of individuals, there remained significant associations between LTL and longevity. Detailed analysis of the longitudinal data set showed that this association was driven by improved survival of individuals with longer LTL over the first 2 years of life. There was no evidence that LTL predicted survival in later adulthood. Our data provide the first evidence from a mammal that LTL can predict mortality and lifespan under natural conditions, and also highlight the potentially dynamic nature of LTL within the lifetimes of individuals experiencing a complex and highly variable environment.