Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
Cell Rep. 2012 Dec 27;2(6):1530-6. doi: 10.1016/j.celrep.2012.11.021.
Telomeric DNA repeats are lost as normal somatic cells replicate. When telomeres reach a critically short length, a DNA damage signal is initiated, inducing cell senescence. Some studies have indicated that telomere length correlates with mortality, suggesting that telomere length contributes to human life span; however, other studies report no correlation, and thus the issue remains controversial. Domestic dogs show parallels in telomere biology to humans, with similar telomere length, telomere attrition, and absence of somatic cell telomerase activity. Using this model, we find that peripheral blood mononuclear cell (PBMC) telomere length is a strong predictor of average life span among 15 different breeds (p < 0.0001), consistent with telomeres playing a role in life span determination. Dogs lose telomeric DNA ~10-fold faster than humans, which is similar to the ratio of average life spans between these species. Breeds with shorter mean telomere lengths show an increased probability of death from cardiovascular disease, which was previously correlated with short telomere length in humans.
端粒 DNA 重复序列在正常体细胞复制时会丢失。当端粒达到临界短长度时,会启动一个 DNA 损伤信号,诱导细胞衰老。一些研究表明,端粒长度与死亡率相关,这表明端粒长度对人类寿命有贡献;然而,其他研究报告没有相关性,因此这个问题仍然存在争议。家犬在端粒生物学上与人类相似,具有相似的端粒长度、端粒损耗和体细胞端粒酶活性缺失。使用这种模型,我们发现外周血单核细胞 (PBMC) 端粒长度是 15 个不同品种平均寿命的强有力预测指标 (p < 0.0001),这与端粒在寿命决定中发挥作用一致。与人类相比,狗失去端粒 DNA 的速度快约 10 倍,这与这两个物种的平均寿命之比相似。端粒长度较短的品种死于心血管疾病的概率增加,这与人类端粒长度较短有关。