衰老、运动能力和 COPD 中的体力活动的分子标志物。

Molecular markers of aging, exercise capacity, & physical activity in COPD.

机构信息

Pulmonary, Allergy, And Critical Care Medicine Section, VA Boston Healthcare System, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.

Pulmonary, Allergy, And Critical Care Medicine Section, VA Boston Healthcare System, Boston, MA, USA.

出版信息

Respir Med. 2021 Oct;187:106576. doi: 10.1016/j.rmed.2021.106576. Epub 2021 Aug 14.

DOI:10.1016/j.rmed.2021.106576

PMID:34416615

Abstract

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 (FEV/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 FEV% 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.

摘要

背景

运动能力（EC）和身体活动（PA）是 COPD 临床结局的独立、潜在可改变的预测因素。生物年龄的分子测量方法可能有助于描述 COPD 患者中观察到的 EC 和 PA 变异性。

方法

在 VA 波士顿的 2 个队列中招募了患有 COPD（FEV/FVC<0.7 或胸部 CT 显示肺气肿）的退伍军人，他们完成了问卷调查、6 分钟步行距离（6MWD）评估运动能力和血液采集。PA 数据（平均每天步数）使用 HJ-720 ITC 计步器收集，采集时间超过 5 天。一部分受试者在 12 周后返回进行重复评估。使用 HumanMethylationEPIC 平台生成 DNA 甲基化数据；使用成熟的算法生成生物年龄和年龄加速的表观遗传估计值。多变量模型调整了年龄、性别、种族、吸烟状况、吸烟包年数、体重指数、队列和估计的细胞计数等因素后，研究了生物年龄、6MWD、PA 与未来急性加重事件（AE）之间的关系。

结果

受试者（n=269）主要为男性（98.5%）、白人（92.9%）和老年人（70.6±8.5 岁），平均 FEV%为 57.7±21.1%，6MWD 为 374.3±93.5m，基线时每日步数为 3043.4±2374 步。在调整后的模型中，基线时多种表观遗传年龄和年龄加速的测量值与 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 年的随访期间，没有任何生物年龄指标与前瞻性 AE 显著相关。