Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
Exp Gerontol. 2018 May;105:47-52. doi: 10.1016/j.exger.2017.10.010. Epub 2017 Oct 12.
Elderly residents of long-term care commonly exhibit a number of age-related health deficits, including impaired physical and cognitive function, chronic illnesses, and chronic inflammation. Given our previous data relating the phenotype and function of innate and adaptive leukocytes from the nursing home elderly to chronic conditions and inflammatory biomarkers, we hypothesized that these factors would influence the regulatory programming of immune cells, thereby contributing to immune dysfunction. Since DNA methylation represents both an important regulatory mechanism of cells as well as a biomarker of health and disease, we sought to characterize the methylome of peripheral blood mononuclear cells (PBMCs) from the nursing home elderly (n=23; 82-98years old, 70% female), and compare these patterns to pathological factors such as dementia, co-morbidity score and frailty, and immune-related factors such as serum C-reactive protein (CRP) and cytokine levels and varicella-zoster virus (VZV) vaccine responsiveness. We show that the most significant changes in DNA methylation levels occurred in relation to co-morbidity score, including one site, cg07725579 (FDR-adjusted p<0.05; closest gene, SIRBP2), and nine DNA methylation regions (Stouffer's p<0.05). DNA methylation age, although not strongly correlated with chronological age, was positively correlated with serum CRP levels (p=0.007), and negatively correlated with vaccine responsiveness (p=0.035). To our knowledge, this study is one of the first to describe associations of DNA methylation patterns with pathological and immune-related factors in residents of long-term care, and may provide important clues pertaining to immune cell dysfunction near the end of life.
长期护理机构的老年居民通常表现出许多与年龄相关的健康缺陷，包括身体和认知功能受损、慢性疾病和慢性炎症。鉴于我们之前的数据表明，养老院老年人的固有和适应性白细胞的表型和功能与慢性疾病和炎症生物标志物有关，我们假设这些因素会影响免疫细胞的调节编程，从而导致免疫功能障碍。由于 DNA 甲基化不仅是细胞的重要调节机制，也是健康和疾病的生物标志物，我们试图描述养老院老年人（n=23；82-98 岁，70%为女性）外周血单核细胞（PBMCs）的甲基组，并将这些模式与痴呆症、合并症评分和虚弱等病理因素以及与免疫相关的因素（如血清 C 反应蛋白（CRP）和细胞因子水平以及水痘带状疱疹病毒（VZV）疫苗反应性）进行比较。我们发现，DNA 甲基化水平的最大变化与合并症评分有关，包括一个位点 cg07725579（经 FDR 调整的 p<0.05；最接近的基因 SIRBP2）和九个 DNA 甲基化区域（Stouffer's p<0.05）。尽管 DNA 甲基化年龄与实际年龄相关性不强，但与血清 CRP 水平呈正相关（p=0.007），与疫苗反应性呈负相关（p=0.035）。据我们所知，这项研究是首次描述长期护理机构居民的 DNA 甲基化模式与病理和免疫相关因素之间的关联之一，可能为生命末期免疫细胞功能障碍提供重要线索。
