Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.
Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.
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白细胞端粒长度的纵向下降，与性别和遗传风险相关。
DOI：
10.18632/aging.100995
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Hägg S
中科院分区：
文献类型：
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作者：
Berglund K;Reynolds CA;Ploner A;Gerritsen L;Hovatta I;Pedersen NL;Hägg S
端粒是位于染色体末端的DNA-蛋白质结构。白细胞端粒长度（LTL）缩短与高龄有关。然而，大多数研究使用横断面数据，因此，我们的研究的目的是模拟纵向轨迹的LTL磨损在20年的老年。在SATSA（瑞典收养/双胞胎衰老研究; N=636人）中通过qPCR进行LTL评估。横截面和纵向协会与年龄进行了估计，后者使用潜在的增长曲线分析。进一步评估LTL的遗传风险评分（GRS）并将其纳入模型中。我们证实了LTL与年龄呈负相关（B=-0.0022 T/S比; 95% CI：-0.0035，-0.0009，p值=0.0008）。经性别调整的纵向LTL分析（1598份样本; ≤5次测量）表明，69岁之前平均下降幅度较小，但69岁后下降速度加快，个体间差异显著。在基线时，女性的平均T/S比单位比LTL长0.6%，纳入GRS改善了模型，其中四个风险等位基因相当于性别之间的效应量差异。在这组老年人中，基线LTL随年龄、性别和遗传背景而变化。LTL的变化率随着年龄的增长而加快，个体间差异很大。
Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=−0.0022 T/S-ratio; 95% CI: −0.0035, −0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ∼6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals.