Background

Exercise capacity (EC) and physical activity (PA) are independent, potentially modifiable predictors of clinical outcomes in COPD. Molecular measures of biological age may help characterize variability in EC and PA observed among COPD patients.

Methods

Veterans with COPD (FEV₁/FVC<0.7 or emphysema on chest computed tomography) enrolled in 2 cohorts at VA Boston completed questionnaires, a 6-min walk distance (6MWD) for EC, and blood collection at enrollment. PA data (average daily step count) was collected using an HJ-720 ITC pedometer over ≥5 days. A subset of subjects returned for repeat assessment after 12 weeks. DNA methylation data was generated using the HumanMethylationEPIC platform; epigenetic estimates of biological age and age acceleration were generated using established algorithms. Multivariable models examined the associations between biological age, 6MWD, PA and future acute exacerbations (AEs), adjusting for chronological age, sex, race, smoking status, pack-years, body mass index, cohort, and estimated cell counts.

Results

Subjects (n = 269) were predominantly male (98.5%), white (92.9%), and elderly (70.6 ± 8.5 years) with average FEV₁% of 57.7 ± 21.1, 6MWD of 374.3 ± 93.5 m, and daily steps of 3043.4 ± 2374 at baseline. In adjusted models, multiple measures of baseline epigenetic age and age acceleration were inversely associated with 6MWD; only GrimAge was inversely associated with PA. Longitudinal change in Hannum-Age was inversely associated with change in EC at 12 weeks (n = 94). No measures of biological age were significantly associated with prospective AEs over 1.3 ± 0.3 years.

Conclusions

Epigenetic measures of biological age are independent predictors of EC and PA, but not AEs, among individuals with COPD.

中文翻译：

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慢性阻塞性肺病患者衰老、运动能力和体力活动的分子标志物

背景

运动能力 (EC) 和身体活动 (PA) 是 COPD 临床结果的独立、潜在可修改的预测因子。生物学年龄的分子测量可能有助于表征在 COPD 患者中观察到的 EC 和 PA 的变异性。

方法

在 VA Boston 的 2 个队列中登记的患有 COPD（FEV ₁ /FVC<0.7 或胸部计算机断层扫描显示肺气肿）的退伍军人完成了问卷调查、EC 的 6 分钟步行距离 (6MWD) 和登记时的血液收集。使用 HJ-720 ITC 计步器在 ≥5 天内收集 PA 数据（平均每日步数）。12 周后，一部分受试者返回进行重复评估。使用 HumanMethylationEPIC 平台生成 DNA 甲基化数据；使用已建立的算法生成生物年龄和年龄加速的表观遗传估计。多变量模型检查了生物学年龄、6MWD、PA 和未来急性发作 (AE) 之间的关联，并根据实际年龄、性别、种族、吸烟状况、包装年数、体重指数、队列和估计的细胞计数进行了调整。

结果

受试者 (n = 269) 主要是男性 (98.5%)、白人 (92.9%) 和老年人 (70.6 ± 8.5 岁)，平均 FEV ₁ % 为 57.7 ± 21.1，6MWD 为 374.3 ± 93.5 m，每日步数为 3043.4 ± 2374 在基线。在调整后的模型中，基线表观遗传年龄和年龄加速的多项测量与 6MWD 呈负相关；只有 GrimAge 与 PA 呈负相关。Hannum-Age 的纵向变化与 12 周时 EC 的变化呈负相关（n = 94）。在 1.3 ± 0.3 年期间，没有任何生物学年龄测量与预期 AE 显着相关。

结论

在 COPD 患者中，生物学年龄的表观遗传测量是 EC 和 PA 的独立预测因子，但不是 AE。