Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America.
PLoS One. 2011;6(6):e14821. doi: 10.1371/journal.pone.0014821. Epub 2011 Jun 22.
From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age in saliva of 34 male identical twin pairs between 21 and 55 years of age. Furthermore, we validated sites in the promoters of three genes and replicated our results in a general population sample of 31 males and 29 females between 18 and 70 years of age. The methylation of three sites--in the promoters of the EDARADD, TOM1L1, and NPTX2 genes--is linear with age over a range of five decades. Using just two cytosines from these loci, we built a regression model that explained 73% of the variance in age, and is able to predict the age of an individual with an average accuracy of 5.2 years. In forensic science, such a model could estimate the age of a person, based on a biological sample alone. Furthermore, a measurement of relevant sites in the genome could be a tool in routine medical screening to predict the risk of age-related diseases and to tailor interventions based on the epigenetic bio-age instead of the chronological age.
从受孕的那一刻起,我们就开始衰老。细胞结构、基因调控和 DNA 序列的衰退会使细胞和生物体衰老。DNA 甲基化模式随年龄的增长而变化,并导致与年龄相关的疾病。在这里,我们在 34 对年龄在 21 至 55 岁之间的男性同卵双胞胎的唾液中鉴定出 88 个基因中的 80 个基因或其附近的 88 个基因,这些基因的胞嘧啶甲基化程度与年龄显著相关。此外,我们在一个年龄在 18 至 70 岁之间的 31 名男性和 29 名女性的普通人群样本中验证了三个基因启动子中的位点,并复制了我们的结果。三个位点——EDARADD、TOM1L1 和 NPTX2 基因启动子中的三个位点——在 50 多年的时间里,随着年龄的增长呈线性甲基化。仅使用这两个基因座中的两个胞嘧啶,我们构建了一个回归模型,该模型可以解释年龄变化的 73%,并且能够以平均 5.2 年的平均精度预测个体的年龄。在法医学中,这样的模型可以仅根据生物样本来估计一个人的年龄。此外,基因组中相关位点的测量可能是常规医疗筛查的一种工具,用于预测与年龄相关的疾病风险,并根据表观遗传生物年龄而不是实际年龄来调整干预措施。
PLoS One. 2011-6-22
Forensic Sci Int Genet. 2017-11
Forensic Sci Int Genet. 2014-7
Int J Epidemiol. 2016-8
Int J Legal Med. 2015-3
PLoS Comput Biol. 2016-11-11
Electrophoresis. 2015-8
Aging Cell. 2010-5-22
Nat Aging. 2025-9-9
MedComm (2020). 2025-9-1
Int J Mol Sci. 2025-7-9
PLoS Genet. 2010-5-27
Genome Res. 2010-1-27
Bioinformatics. 2009-3-15
BMC Bioinformatics. 2008-12-29
PLoS Comput Biol. 2008-8-15
PLoS One. 2008-7-16