Verschoor Chris P, McEwen Lisa M, Kohli Vikas, Wolfson Christina, Bowdish Dawn Me, Raina Parminder, Kobor Michael S, Balion Cynthia
Department of Pathology and Molecular Medicine, McMaster University, 1280 Main St. W, MIP309A, Hamilton, ON, Canada.
McMaster Institute for Research on Aging, McMaster University, Hamilton, ON, Canada.
BMC Genet. 2017 Jun 21;18(1):57. doi: 10.1186/s12863-017-0525-3.
The levels of circulating cytokines fluctuate with age, acute illness, and chronic disease, and are predictive of mortality; this is also true for patterns of DNA (CpG) methylation. Given that immune cells are particularly sensitive to changes in the concentration of cytokines in their microenvironment, we hypothesized that serum levels of TNF, IL-6, IL-8 and IL-10 would correlate with genome-wide alterations in the DNA methylation levels of blood leukocytes. To test this, we evaluated community-dwelling adults (n = 14; 48-78 years old) recruited to a pilot study for the Canadian Longitudinal Study on Aging (CLSA), examining DNA methylation patterns in peripheral blood mononuclear cells using the Illumina HumanMethylation 450 K BeadChip.
We show that, apart from age, serum IL-10 levels exhibited the most substantial association to DNA methylation patterns, followed by TNF, IL-6 and IL-8. Furthermore, while the levels of these cytokines were higher in elderly adults, no associations with epigenetic accelerated aging, derived using the epigenetic clock, were observed.
As a preliminary study with a small sample size, the conclusions drawn from this work must be viewed with caution; however, our observations are encouraging and certainly warrant more suitably powered studies of this relationship.
循环细胞因子水平会随年龄、急性疾病和慢性疾病而波动,并且可预测死亡率;DNA(CpG)甲基化模式也是如此。鉴于免疫细胞对其微环境中细胞因子浓度的变化特别敏感,我们推测血清肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和白细胞介素-10(IL-10)水平与血液白细胞DNA甲基化水平的全基因组改变相关。为了验证这一点,我们评估了招募到加拿大老龄化纵向研究(CLSA)试点研究中的社区居住成年人(n = 14;48 - 78岁),使用Illumina HumanMethylation 450K芯片检测外周血单个核细胞中的DNA甲基化模式。
我们发现,除年龄外,血清IL-10水平与DNA甲基化模式的关联最为显著,其次是TNF、IL-6和IL-8。此外,虽然这些细胞因子在老年人中水平较高,但未观察到与使用表观遗传时钟得出的表观遗传加速衰老存在关联。
作为一项样本量较小的初步研究,这项工作得出的结论必须谨慎看待;然而,我们的观察结果令人鼓舞,当然值得对这种关系进行更有充分说服力的研究。