Moore Ann Zenobia, Hernandez Dena G, Tanaka Toshiko, Pilling Luke C, Nalls Mike A, Bandinelli Stefania, Singleton Andrew B, Ferrucci Luigi
Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland.
J Gerontol A Biol Sci Med Sci. 2016 Aug;71(8):1029-35. doi: 10.1093/gerona/glv118. Epub 2015 Sep 9.
Patterns of DNA methylation (DNAm) that track with aging have been identified. However, the relevance of these patterns for aging outcomes remains unclear. Longitudinal epigenome-wide DNAm information was obtained from the InCHIANTI study, a large representative European population. DNAm was evaluated using the Illumina HumanMethylation450 array on blood samples collected at baseline and 9-year follow-up: observations from 499 participants with paired longitudinal blood sample and information on differential blood count were included in analyses. A total of 56,579 markers were significantly associated with age in cross-sectional analysis of DNAm at year 9, 31,252 markers were changed significantly over the 9-year follow-up, and 16,987 markers were both cross-sectionally associated with age and significantly changed over time. Rates of change at 76 markers and year 9 level of DNAm at 88 markers were identified as strongly associated with mortality in Cox proportional hazard models adjusted for age and relevant covariates (mean follow-up time 4.4 years). Less than 0.05% of markers associated with age or that changed over time were also associated with mortality after adjusting for chronological age. Although the influence of DNAm on health and longevity remains unclear, these findings confirm that aging is associated cross-sectionally and longitudinally with robust and consistent patterns of methylation change.
与衰老相关的DNA甲基化（DNAm）模式已被识别。然而，这些模式与衰老结果之间的相关性仍不明确。纵向全表观基因组DNAm信息来自于InCHIANTI研究，这是一个具有代表性的欧洲大样本人群。在基线和9年随访时采集的血样上，使用Illumina HumanMethylation450芯片评估DNAm：分析纳入了499名有配对纵向血样且有血细胞计数差异信息的参与者的观察数据。在第9年DNAm的横断面分析中，共有56,579个标记与年龄显著相关，在9年随访期间有31,252个标记发生了显著变化，16,987个标记既在横断面与年龄相关，又随时间发生了显著变化。在调整年龄和相关协变量的Cox比例风险模型中，76个标记的变化率和88个标记在第9年的DNAm水平被确定与死亡率密切相关（平均随访时间4.4年）。在调整了实足年龄后，与年龄相关或随时间变化的标记中，与死亡率相关的标记不到0.05%。虽然DNAm对健康和长寿的影响仍不明确，但这些发现证实，衰老在横断面和纵向上都与强大且一致的甲基化变化模式相关。
