Molecular markers of aging, exercise capacity, & physical activity in COPD.
Molecular markers of aging, exercise capacity, & physical activity in COPD.
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衰老、运动能力的分子标记，
DOI：
10.1016/j.rmed.2021.106576
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发表时间：
2021
影响因子：
4.3
通讯作者：
Moy,MarilynL
中科院分区：
文献类型：
--
作者：
Wan,EmilyS;Goldstein,RebekahL;Garshick,Eric;DeMeo,DawnL;Moy,MarilynL
背景运动能力（EC）和体力活动（PA）是COPD临床预后的独立、潜在可改变的预测因子。分子生物学年龄的措施可能有助于表征变异EC和PA之间观察到的COPD patients.MethodsVeterans与COPD（FEV 1/FVC<0.7或肺气肿胸部计算机断层扫描）在VA波士顿2个队列参加完成问卷调查，6分钟步行距离（6 MWD）EC，并在登记时采血。使用HJ-720 ITC计步器收集≥5天的PA数据（平均每日步数）。一部分受试者在12周后返回接受重复评估。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学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、6 MWD、PA和未来急性加重（AE）之间的相关性，调整了实足年龄、性别、种族、吸烟状况、包年、体重指数、队列和估计的细胞计数。（98.5%）、白色（92.9%）和老年人（70.6 ± 8.5岁），基线时平均FEV1%为57.7 ± 21.1，6 MWD为374.3 ± 93.5 m，每日步数为3043.4 ± 2374。在调整后的模型中，基线表观遗传年龄和年龄加速的多项指标与6 MWD呈负相关;只有GrimAge与PA呈负相关。汉纳姆年龄的纵向变化与12周时EC的变化呈负相关（n = 94）。没有措施的生物学年龄显着相关的前瞻性AE超过1.3 ± 0.3 years.ConclusionsEpigenetic措施的生物学年龄是独立的预测EC和PA，但不AE，在COPD患者。
BackgroundExercise 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.MethodsVeterans 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.ResultsSubjects (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.ConclusionsEpigenetic measures of biological age are independent predictors of EC and PA, but not AEs, among individuals with COPD.