Arpón Ana, Milagro Fermín I, Santos José L, García-Granero Marta, Riezu-Boj José-Ignacio, Martínez J Alfredo
Department of Nutrition, Food Sciences and Physiology, University of Navarra, Pamplona, Spain.
Centre for Nutrition Research, University of Navarra, Pamplona, Spain.
Front Endocrinol (Lausanne). 2019 Jul 17;10:496. doi: 10.3389/fendo.2019.00496. eCollection 2019.
The distribution of adipose tissue is influenced by gender and by age, shifting from subcutaneous to visceral depots with longevity, increasing the development of several aging-related diseases and manifestations such as obesity, metabolic syndrome, and insulin resistance. Epigenetics might have an important role in aging processes. The aim of this research was to investigate the interactions between aging and epigenetic processes and the role of visceral adipose tissue, insulin resistance, and dyslipidaemia. Two different study samples of 366 and 269 adult participants were analyzed. Anthropometric, biochemical (including the triglycerides-glucose (TyG) index), and blood pressure measurements were assessed following standardized methods. Body composition measurements by Dual-energy X-ray absorptiometry (DXA) were also performed for the second sample. Methylation data were assessed by Infinium Human Methylation BeadChip (Illumina) in peripheral white blood cells. Epigenetic age acceleration was calculated using the methods DNAmAge (AgeAcc) and GrimAge (AgeAccGrim). Age acceleration (AgeAccGrim) showed better correlations than AgeAcc with most of the measured variables (waist circumference, glucose, HOMA-IR, HDL-cholesterol, triglycerides, and TyG index) for the first sample. In the second sample, all the previous correlations were confirmed, except for HOMA-IR. In addition, many of the anthropometrical measurements assessed by DXA and C-reactive protein (CRP) were also statistically associated with AgeAccGrim. Associations separated by sex showed statistically significant correlations between AgeAccGrim and HDL-cholesterol or CRP in women, whereas, in men, the association was with visceral adipose tissue mass DXA, triglycerides and TyG index. Linear regression models (model 1 included visceral adipose tissue mass DXA and TyG index and model 2 included HDL-cholesterol and CRP) showed a significant association for men concerning visceral adipose tissue mass DXA and TyG index, while HDL-cholesterol and CRP were associated in women. Moreover, structural equation modeling showed that the TyG index was mediating the majority of the visceral adipose tissue mass action on age acceleration. Collectively, these findings showed that there are different mechanisms affecting epigenetic age acceleration depending on sex. The identified relationships between epigenetic age acceleration and disease markers will contribute to the understanding of the development of age-related diseases.
脂肪组织的分布受性别和年龄影响，随着年龄增长，脂肪组织会从皮下储存部位转移至内脏储存部位，从而增加肥胖、代谢综合征和胰岛素抵抗等多种与衰老相关疾病及症状的发生风险。表观遗传学可能在衰老过程中发挥重要作用。本研究旨在探讨衰老与表观遗传过程之间的相互作用，以及内脏脂肪组织、胰岛素抵抗和血脂异常的作用。对366名和269名成年参与者的两个不同研究样本进行了分析。按照标准化方法评估人体测量学指标、生化指标（包括甘油三酯 - 葡萄糖（TyG）指数）和血压测量值。还对第二个样本进行了双能X线吸收法（DXA）测量身体成分。通过Illumina公司的Infinium Human Methylation BeadChip对外周血白细胞中的甲基化数据进行评估。使用DNAmAge（AgeAcc）和GrimAge（AgeAccGrim）方法计算表观遗传年龄加速。对于第一个样本，年龄加速（AgeAccGrim）与大多数测量变量（腰围、血糖、HOMA - IR、高密度脂蛋白胆固醇、甘油三酯和TyG指数）的相关性比AgeAcc更好。在第二个样本中，除了HOMA - IR外，所有先前的相关性均得到证实。此外，通过DXA评估的许多人体测量指标和C反应蛋白（CRP）也与AgeAccGrim存在统计学关联。按性别划分的关联显示，AgeAccGrim与女性的高密度脂蛋白胆固醇或CRP之间存在统计学显著相关性，而在男性中，这种关联则与内脏脂肪组织质量DXA、甘油三酯和TyG指数有关。线性回归模型（模型1包括内脏脂肪组织质量DXA和TyG指数，模型2包括高密度脂蛋白胆固醇和CRP）显示，男性的内脏脂肪组织质量DXA和TyG指数存在显著关联，而女性则与高密度脂蛋白胆固醇和CRP有关。此外，结构方程模型表明，TyG指数介导了内脏脂肪组织质量对年龄加速的大部分作用。总体而言，这些发现表明，根据性别不同，影响表观遗传年龄加速的机制也不同。表观遗传年龄加速与疾病标志物之间已确定的关系将有助于理解与年龄相关疾病的发展。
