握力与 DNA 甲基化年龄加速呈负相关。
Grip strength is inversely associated with DNA methylation age acceleration.
机构信息
Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.
Michigan Institute for Health Policy and Innovation (IHPI), Ann Arbor, MI, USA.
出版信息
J Cachexia Sarcopenia Muscle. 2023 Feb;14(1):108-115. doi: 10.1002/jcsm.13110. Epub 2022 Nov 9.
BACKGROUND
There is a large body of evidence linking muscular weakness, as determined by low grip strength, to a host of negative ageing-related health outcomes. Given these links, grip strength has been labelled a 'biomarker of aging'; and yet, the pathways connecting grip strength to negative health consequences are unclear. The objective of this study was to determine whether grip strength was associated with measures of DNA methylation (DNAm) age acceleration.
METHODS
Middle age and older adults from the 2006 to 2008 waves of the Health and Retirement Study with 8-10 years of follow-up were included. Cross-sectional and longitudinal regression modelling was performed to examine the association between normalized grip strength (NGS) and three measures of DNAm age acceleration, adjusting for cell composition, sociodemographic variables and smoking. Longitudinal modelling was also completed to examine the association between change in absolute grip strength and DNAm age acceleration. The three DNAm clocks used for estimating age acceleration include the established DunedinPoAm, PhenoAge and GrimAge clocks.
RESULTS
There was a robust and independent cross-sectional association between NGS and DNAm age acceleration for men using the DunedinPoAm (β: -0.36; P < 0.001), PhenoAge (β: -8.27; P = 0.01) and GrimAge (β: -4.56; P = 0.01) clocks and for women using the DunedinPoAm (β: -0.36; P < 0.001) and GrimAge (β: -4.46; P = 0.01) clocks. There was also an independent longitudinal association between baseline NGS and DNAm age acceleration for men (β: -0.26; P < 0.001) and women (β: -0.36; P < 0.001) using the DunedinPoAm clock and for women only using the PhenoAge (β: -8.20; P < 0.001) and GrimAge (β: -5.91; P < 0.001) clocks. Longitudinal modelling revealed a robust association between change in grip strength from wave 1 to wave 3 was independently associated with PhenoAgeAA (β: -0.13; 95% CI: -0.23, -0.03) and GrimAgeAA (β: -0.07; 95% CI: -0.14, -0.01) in men only (both P < 0.05).
CONCLUSIONS
Our findings provide some initial evidence of age acceleration among men and women with lower NGS and loss of strength over time. Future research is needed to understand the extent to which DNAm age mediates the association between grip strength and chronic disease, disability and mortality.
背景
大量证据表明，肌肉力量较弱（通过握力测定）与许多与衰老相关的负面健康结果有关。鉴于这些关联，握力已被标记为“衰老的生物标志物”；然而，将握力与负面健康后果联系起来的途径尚不清楚。本研究的目的是确定握力是否与 DNA 甲基化（DNAm）年龄加速有关。
方法
纳入了来自 2006 年至 2008 年健康与退休研究中具有 8-10 年随访的中年和老年人，使用交叉和纵向回归模型来检验标准化握力（NGS）与三种 DNAm 年龄加速指标之间的关联，同时调整细胞成分、社会人口统计学变量和吸烟。还进行了纵向建模，以检验绝对握力变化与 DNAm 年龄加速之间的关联。用于估计年龄加速的三个 DNAm 时钟包括已建立的 DunedinPoAm、PhenoAge 和 GrimAge 时钟。
结果
对于男性，使用 DunedinPoAm（β：-0.36；P<0.001）、PhenoAge（β：-8.27；P=0.01）和 GrimAge（β：-4.56；P=0.01）时钟，以及对于女性，使用 DunedinPoAm（β：-0.36；P<0.001）和 GrimAge（β：-4.46；P=0.01）时钟，NGS 与 DNAm 年龄加速之间存在稳健且独立的横断面关联。对于男性（β：-0.26；P<0.001）和女性（β：-0.36；P<0.001），使用 DunedinPoAm 时钟以及仅对于女性，使用 PhenoAge（β：-8.20；P<0.001）和 GrimAge（β：-5.91；P<0.001）时钟，基线 NGS 与 DNAm 年龄加速之间也存在独立的纵向关联。纵向建模显示，从第 1 波到第 3 波的握力变化与 PhenoAgeAA（β：-0.13；95%CI：-0.23，-0.03）和 GrimAgeAA（β：-0.07；95%CI：-0.14，-0.01）之间存在稳健的关联，仅在男性中（均 P<0.05）。
结论
我们的发现为男性和女性中较低的 NGS 和随时间推移的力量丧失与年龄加速之间提供了一些初步证据。需要进一步研究以了解 DNAm 年龄在多大程度上介导握力与慢性疾病、残疾和死亡率之间的关联。
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