The Dartmouth Institute for Health Policy, Williamson Translational Research Bld, 5., 1 Medical Center Drive, Lebanon, NH, 03766, USA.
Quantitative Biomedical Sciences Program, Dartmouth, Hanover, NH, USA.
Clin Epigenetics. 2021 Mar 2;13(1):46. doi: 10.1186/s13148-021-01031-7.
Assessing functional ability is an important component of understanding healthy aging. Objective measures of functional ability include grip strength, gait speed, sit-to-stand time, and 6-min walk distance. Using samples from a weight loss clinical trial in older adults with obesity, we examined the association between changes in physical function and DNA-methylation-based biological age at baseline and 12 weeks in 16 individuals. Peripheral blood DNA methylation was measured (pre/post) with the Illumina HumanMethylationEPIC array and the Hannum, Horvath, and PhenoAge DNA methylation age clocks were used. Linear regression models adjusted for chronological age and sex tested the relationship between DNA methylation age and grip strength, gait speed, sit-to-stand, and 6-min walk.
Participant mean weight loss was 4.6 kg, and DNA methylation age decreased 0.8, 1.1, and 0.5 years using the Hannum, Horvath, and PhenoAge DNA methylation clocks respectively. Mean grip strength increased 3.2 kg. Decreased Hannum methylation age was significantly associated with increased grip strength (β = -0.30, p = 0.04), and increased gait speed (β = 0.02, p = 0.05), in adjusted models. Similarly, decreased methylation age using the PhenoAge clock was associated with significantly increased gait speed (β = 0.02, p = 0.04). A decrease in Horvath DNA methylation age and increase in physical functional ability did not demonstrate a significant association.
The observed relationship between increased physical functional ability and decreased biological age using DNA methylation clocks demonstrate the potential utility of DNA methylation clocks to assess interventional approaches to improve health in older obese adults.
National Institute on Aging (NIA), NCT03104192. Posted April 7, 2017, https://clinicaltrials.gov/ct2/show/NCT03104192.
评估功能能力是了解健康老龄化的一个重要组成部分。功能能力的客观测量包括握力、步速、从座位到站立的时间和 6 分钟步行距离。我们使用肥胖老年人减肥临床试验的样本，在 16 名个体中检查了基线和 12 周时身体功能变化与 DNA 甲基化生物年龄之间的关联。使用 Illumina HumanMethylationEPIC 阵列测量外周血 DNA 甲基化，使用 Hannum、Horvath 和 PhenoAge DNA 甲基化时钟测量 DNA 甲基化年龄。线性回归模型调整了年龄和性别，测试了 DNA 甲基化年龄与握力、步速、从座位到站立的时间和 6 分钟步行的关系。
参与者的平均体重减轻了 4.6 公斤，使用 Hannum、Horvath 和 PhenoAge DNA 甲基化时钟，DNA 甲基化年龄分别减少了 0.8、1.1 和 0.5 岁。平均握力增加了 3.2 公斤。调整后的模型中，Hannum 甲基化年龄降低与握力增加显著相关（β=-0.30，p=0.04），与步速增加显著相关（β=0.02，p=0.05）。同样，使用 PhenoAge 时钟，甲基化年龄降低与步速显著增加相关（β=0.02，p=0.04）。Horvath DNA 甲基化年龄降低与身体功能能力增加之间没有显著关联。
观察到的身体功能能力增加与 DNA 甲基化时钟的生物年龄降低之间的关系表明，DNA 甲基化时钟在评估改善老年肥胖人群健康的干预方法方面具有潜在的应用价值。
美国国立卫生研究院（NIA），NCT03104192。于 2017 年 4 月 7 日发布，https://clinicaltrials.gov/ct2/show/NCT03104192。
