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较短的端粒与携带载脂蛋白Eε4且患有痴呆症的人群的死亡率相关。

Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia.

作者信息

Honig Lawrence S, Schupf Nicole, Lee Joseph H, Tang Ming X, Mayeux Richard

机构信息

Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center, New York, NY, USA.

出版信息

Ann Neurol. 2006 Aug;60(2):181-7. doi: 10.1002/ana.20894.

Abstract

OBJECTIVE

Reduced telomere length may be a marker of biological aging. We hypothesized that telomere length might thus relate to increased risk for dementia and mortality.

METHODS

This nested case-control study used stored leukocyte DNA from 257 individuals (mean age, 81.4 +/- 7.9 years; 64.6% female; 44.7% Hispanic, 33.5% non-Hispanic black, and 21.8% non-Hispanic white). Our assay used real-time polymerase chain reaction, with two separate reactions amplifying telomere sequence and reference single copy gene (ribosomal-protein-P0), providing a calculated telomere-to-single copy gene (T/S) ratio.

RESULTS

Mean telomere length was shorter among subjects dying during follow-up than in those surviving (0.453 +/- 0.211 vs 0.525 +/- 0.226 [+/- standard deviation]; p < 0.009). It was also shorter in those with Alzheimer's disease compared with control subjects (0.458 +/- 0.207 vs 0.516 +/- 0.229; p < 0.03). For participants with Alzheimer's disease, compared with those with the longest telomeres, the mortality odds ratio (OR) was 4.8 (95% confidence interval [CI], 1.7-13.8) in those with intermediate-length telomeres and 7.3 (95% CI, 2.4-22.0) in those with the shortest telomeres. The presence of an epsilon4 allele also increased the mortality OR, with an OR of 5.8 (95% CI, 1.3-26.4) for intermediate-length telomeres and an OR of 9.0 (95% CI, 1.9-41) for the shortest telomeres.

INTERPRETATION

Our findings suggest that leukocyte telomere length is related to both dementia and mortality and may be a marker of biological aging.

摘要

目的

端粒长度缩短可能是生物衰老的一个标志。我们推测端粒长度可能因此与痴呆症和死亡率风险增加有关。

方法

这项巢式病例对照研究使用了257名个体(平均年龄81.4±7.9岁;64.6%为女性;44.7%为西班牙裔,33.5%为非西班牙裔黑人,21.8%为非西班牙裔白人)储存的白细胞DNA。我们的检测使用实时聚合酶链反应,通过两个独立反应扩增端粒序列和参考单拷贝基因(核糖体蛋白P0),得出计算的端粒与单拷贝基因(T/S)比值。

结果

随访期间死亡的受试者的平均端粒长度比存活者短(0.453±0.211对0.525±0.226[±标准差];p<0.009)。与对照受试者相比,阿尔茨海默病患者的端粒长度也较短(0.458±0.207对0.516±0.229;p<0.03)。对于患有阿尔茨海默病的参与者,与端粒最长的参与者相比,端粒长度中等的参与者的死亡比值比(OR)为4.8(95%置信区间[CI],1.7 - 13.8),端粒最短的参与者的死亡比值比为7.3(95%CI,2.4 - 22.0)。ε4等位基因的存在也增加了死亡OR,端粒长度中等的参与者的OR为5.8(95%CI,1.3 - 26.4),端粒最短的参与者的OR为9.0(95%CI,1.9 - 41)。

解读

我们的研究结果表明白细胞端粒长度与痴呆症和死亡率均有关,可能是生物衰老的一个标志。

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