期刊
AGING-US
卷 8, 期 2, 页码 394-401出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100908
关键词
DNA-methylation; epigenetic; aging; age; prediction; predictor; survival; mortality; PDE4C; CLCN6
资金
- Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award)
- Wellcome Trust Institutional Strategic Support Fund
- University of Edinburgh
- University of Queensland
- Else Kroner-Fresenius Stiftung [2010_A96, 2014_A193]
- German Research Foundation (DFG) [WA 1706/2-1]
- German Ministry of Education and Research (BMBF)
- German Ministry of Education and Research (OBELICS)
- Interdisciplinary Center for Clinical Research (IZKF) within the faculty of Medicine at the RWTH Aachen University [O1-1]
- University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative [MR/K026992/1]
- United Kingdom Biotechnology and Biological Sciences Research Council (BBSRC)
- Medical Research Council (MRC)
- Age UK
- Medical Research Council [MR/K026992/1] Funding Source: researchfish
DNA-methylation (DNAm) levels at age-associated CpG sites can be combined into epigenetic aging signatures to estimate donor age. It has been demonstrated that the difference between such epigenetic age-predictions and chronological age is indicative for of all-cause mortality in later life. In this study, we tested alternative epigenetic signatures and followed the hypothesis that even individual age-associated CpG sites might be indicative for life-expectancy. Using a 99-CpG aging model, a five-year higher age-prediction was associated with 11% greater mortality risk in DNAm profiles of the Lothian Birth Cohort 1921 study. However, models based on three CpGs, or even individual CpGs, generally revealed very high offsets in age-predictions if applied to independent microarray datasets. On the other hand, we demonstrate that DNAm levels at several individual age-associated CpGs seem to be associated with life expectancy - e.g., at CpGs associated with the genes PDE4C and CLCN6. Our results support the notion that small aging signatures should rather be analysed by more quantitative methods, such as site-specific pyrosequencing, as the precision of age-predictions is rather low on independent microarray datasets. Nevertheless, the results hold the perspective that simple epigenetic biomarkers, based on few or individual age-associated CpGs, could assist the estimation of biological age.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据