Association of shorter leucocyte telomere length with risk of frailty.
Association of shorter leucocyte telomere length with risk of frailty.
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DOI：
10.1002/jcsm.12971
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发表时间：
2022-06
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衰弱是一种多维度的衰弱综合症，影响多个系统并容易导致不良的健康结果。尽管实际年龄是主要的风险因素，但个体间的风险差异尚未完全了解。白细胞端粒长度（LTL）是生物年龄的一个拟议标志，与许多疾病的风险有关。我们试图确定零担是否与虚弱风险相关。我们利用了 441781 名英国生物银行参与者（年龄 40-69 岁）的横截面数据，以及有关虚弱指标和 LTL 的完整数据。虚弱被定义为存在五个指标中的至少三个：握力较弱、行走速度较慢、过去一年体重减轻、体力活动减少以及过去两周疲惫不堪。 LTL 使用经过验证的 qPCR 方法进行测量，并报告为端粒重复次数 (T) 与单拷贝基因 (S) 的比率（T/S 比率）。使用调整后的（实际年龄、性别、剥夺、吸烟、饮酒、体重指数和多发病）多项和序数回归模型评估 LTL 与虚弱的关联，结果分别以相对风险 (RRR) 或比值比 (OR) 以及 95% 置信区间 (CI) 表示。孟德尔随机化 (MR) 使用 131 个与 LTL 相关的遗传变异来评估 LTL 与虚弱之间是否存在因果关系。体弱的参与者 (4.6%) 年龄较大（中位年龄差异 (95% CI)：3 (2.5; 3.5) 岁，P = 2.73 × 10−33），更有可能是女性（61%，P = 1.97 × 10−129），并且 LTL 较短（−0.13SD 与 0.03SD， P = 5.43 × 10−111) 比非虚弱者强。在调整分析中，年龄和 LTL 均与虚弱相关（实际年龄每增加一年，RRR = 1.03 (95% CI: 1.02; 1.04)，P = 3.99 × 10−12；每 SD 缩短 LTL 1.10 (1.08; 1.11)，P = 1.46 × 10−30)。在每个年龄组（40-49、50-59、60-69 岁）中，端粒较短 (-2SD) 的参与者与端粒较长 (+2SD) 的参与者相比，衰弱发生率高出约 33%。 MR 分析显示 LTL 与虚弱之间的关联与观察相关性方向一致，但不具有统计学显着性（MR 中位数：OR (95% CI)：每 SD 较短的 LTL 为 1.08 (0.98; 1.19)，P = 0.13）。 LTL 的个体间差异与虚弱风险相关，与实际年龄和其他危险因素无关。我们的研究结果为衰弱的另一个生物决定因素提供了证据。
Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter‐individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. We utilized cross‐sectional data from 441 781 UK Biobank participants (aged 40–69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single‐copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10−33), more likely to be female (61%, P = 1.97 × 10−129), and had shorter LTL (−0.13SD vs. 0.03SD, P = 5.43 × 10−111) than non‐frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10−12; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10−30). Within each age group (40–49, 50–59, 60–69 years), the prevalence of frailty was about 33% higher in participants with shorter (−2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR‐Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13). Inter‐individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.
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作者：
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DOI：
10.1098/rstb.2016.0436
发表时间：
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期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
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