Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
Neurosci Lett. 2011 Mar 29;492(1):15-8. doi: 10.1016/j.neulet.2011.01.041. Epub 2011 Feb 2.
Telomeres are short DNA repeats on the ends of mammalian chromosomes, which can undergo incomplete replication leading to gradual shortening with each cell cycle. Age and oxidative stress are contributors to telomere shortening; thus, telomere length may be a composite measure of biologic aging, and a potential predictor of health status in older adults. We evaluated whether relative telomere length (the proportion of telomere repeat copy number to single gene copy number, using a real-time PCR method) predicts cognitive decline measured ten years later among ∼ 2000 older participants in the Nurses' Health Study (NHS). Mixed linear regression was used to evaluate mean differences in cognitive decline according to telomere length. After adjustment for potential confounders, we found that decreasing telomere length was associated with more cognitive decline, although associations were modest (e.g. for a global score, averaging all six tests in our cognitive battery, mean difference=0.03 standard units per SD increase in telomere length; p=0.04). The magnitude of these estimates was similar to the differences we find in this cohort for women one year apart in age (e.g. the differences that we observe between women who are 73 versus 74 years of age); thus, our results suggest that telomere length is not a particularly powerful marker of impending cognitive decline.
端粒是哺乳动物染色体末端的短 DNA 重复序列，在每个细胞周期中，端粒会经历不完全复制，导致端粒逐渐缩短。年龄和氧化应激是端粒缩短的因素；因此，端粒长度可能是生物衰老的综合衡量标准，也是老年人健康状况的潜在预测指标。我们评估了相对端粒长度（使用实时 PCR 方法，端粒重复序列数量与单个基因数量的比例）是否可以预测 10 年后护士健康研究（NHS）中约 2000 名老年参与者的认知能力下降。混合线性回归用于根据端粒长度评估认知能力下降的平均差异。在调整潜在混杂因素后，我们发现端粒长度的缩短与认知能力下降有关，尽管关联较弱（例如，对于全球评分，对我们认知测试中的所有六个测试进行平均，端粒长度每增加一个标准差，平均差异为 0.03 个标准单位；p=0.04）。这些估计值的幅度与我们在该队列中发现的年龄相差一年的女性之间的差异相似（例如，我们观察到 73 岁和 74 岁女性之间的差异）；因此，我们的结果表明，端粒长度不是即将发生的认知能力下降的特别有力的标志物。
