Centre for Biodiversity Dynamics, Institute for Biology, Norwegian University for Science and Technology, 7014 Trondheim, Norway;
Institute of Evolutionary Biology, School of Biological Sciences, University of Edinburgh, EH9 3FL Edinburgh, United Kingdom.
Proc Natl Acad Sci U S A. 2021 Apr 13;118(15). doi: 10.1073/pnas.2020563118.
Telomere length (TL) is considered an important biomarker of whole-organism health and aging. Across humans and other vertebrates, short telomeres are associated with increased subsequent mortality risk, but the processes responsible for this correlation remain uncertain. A key unanswered question is whether TL-mortality associations arise due to positive effects of genes or early-life environment on both an individual's average lifetime TL and their longevity, or due to more immediate effects of environmental stressors on within-individual TL loss and increased mortality risk. Addressing this question requires longitudinal TL and life history data across the entire lifetimes of many individuals, which are difficult to obtain for long-lived species like humans. Using longitudinal data and samples collected over nearly two decades, as part of a long-term study of wild Soay sheep, we dissected an observed positive association between TL and subsequent survival using multivariate quantitative genetic models. We found no evidence that telomere attrition was associated with increased mortality risk, suggesting that TL is not an important marker of biological aging or exposure to environmental stress in our study system. Instead, we find that among-individual differences in average TL are associated with increased lifespan. Our analyses suggest that this correlation between an individual's average TL and lifespan has a genetic basis. This demonstrates that TL has the potential to evolve under natural conditions, and suggests an important role of genetics underlying the widespread observation that short telomeres predict mortality.
端粒长度 (TL) 被认为是衡量整体生物健康和衰老的重要生物标志物。在人类和其他脊椎动物中，短端粒与随后的死亡率风险增加有关，但导致这种相关性的过程仍不确定。一个关键的未解决问题是，TL 与死亡率的关联是由于基因或早期环境对个体平均寿命 TL 和长寿的积极影响，还是由于环境压力对个体 TL 损失和死亡率风险增加的更直接影响。要解决这个问题，需要在许多个体的整个生命周期内获得纵向 TL 和生命史数据，对于像人类这样的长寿物种来说，这是很难获得的。利用 20 多年来收集的纵向数据和样本，作为对野生斯澳羊进行的一项长期研究的一部分，我们使用多变量数量遗传学模型来剖析 TL 与随后的生存之间观察到的正相关关系。我们没有发现端粒损耗与死亡率风险增加有关的证据，这表明在我们的研究系统中，TL 不是生物衰老或暴露于环境压力的重要标志物。相反，我们发现平均 TL 个体间差异与寿命延长有关。我们的分析表明，个体平均 TL 与寿命之间的这种相关性具有遗传基础。这表明 TL 有可能在自然条件下进化，并表明遗传在广泛观察到的短端粒预测死亡率的现象中起着重要作用。
