全基因组甲基化谱揭示了人类衰老速度的定量观点。
Genome-wide methylation profiles reveal quantitative views of human aging rates.
机构信息
Department of Bioengineering, University of California, San Diego, CA 92093, USA.
Sage Bionetworks, Seattle, WA 98109, USA.
出版信息
Mol Cell. 2013 Jan 24;49(2):359-367. doi: 10.1016/j.molcel.2012.10.016. Epub 2012 Nov 21.
The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Here, we build a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual's methylome ages, which we show is impacted by gender and genetic variants. We also show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. Moreover, we show how our aging model is upheld in other human tissues and reveals an advanced aging rate in tumor tissue. Our model highlights specific components of the aging process and provides a quantitative readout for studying the role of methylation in age-related disease.
从分子谱中衡量人类衰老的能力在许多领域具有实际意义，包括疾病预防和治疗、法医学以及寿命延长。尽管年龄与 DNA 甲基化的变化有关，但甲基组尚未用于衡量和比较人类衰老速度。在这里，我们使用来自 656 个人的全血中的超过 450,000 个 CpG 标记物构建了一个定量衰老模型，这些人年龄在 19 岁至 101 岁之间。该模型衡量了个体甲基组衰老的速度，我们发现这受到性别和遗传变异的影响。我们还表明，衰老速度的差异有助于解释表观遗传漂移，并反映在转录组中。此外，我们展示了我们的衰老模型在其他人体组织中的表现，并揭示了肿瘤组织中衰老速度的加快。我们的模型突出了衰老过程的特定组成部分，并为研究甲基化在与年龄相关的疾病中的作用提供了定量读数。
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