DunedinPACE, a DNA methylation biomarker of the pace of aging.
DunedinPACE, a DNA methylation biomarker of the pace of aging.
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DOI：
10.7554/elife.73420
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发表时间：
2022-01-14
期刊：
影响因子：
7.7
通讯作者：
Moffitt TE
中科院分区：
文献类型：
--
作者：
Belsky DW;Caspi A;Corcoran DL;Sugden K;Poulton R;Arseneault L;Baccarelli A;Chamarti K;Gao X;Hannon E;Harrington HL;Houts R;Kothari M;Kwon D;Mill J;Schwartz J;Vokonas P;Wang C;Williams BS;Moffitt TE
需要采取措施来量化干预措施对生物衰老速度的影响，以评估人类的老年保护干预措施。以前，我们表明，从DNA甲基化血液测试中量化生物衰老的速度是可能的（Belsky等人，2020年）。在这里，我们报告了下一代衰老速度的DNA甲基化生物标志物，DunedinPACE（从表观基因组计算的衰老速度）。我们使用1972-1973年达尼丁出生队列研究的数据，追踪了二十年内四个时间点19项器官系统完整性指标的个体内下降情况，以模拟衰老速度。我们使用弹性网络回归和DNA甲基化数据集将这二十年的衰老速度提炼成单时间点DNA甲基化血液测试，该数据集限于排除具有低重测可靠性的探针。我们在另外五个数据集中评估了由此产生的措施，名为DunedinPACE。DunedinPACE显示出较高的重测信度，与发病率、残疾和死亡率相关，并表明童年逆境的年轻人衰老速度更快。DunedinPACE的效果大小类似于GrimAge Clock的效果大小。在对事件发病率、残疾和死亡率的分析中，DunedinPACE和GrimAge增加了增量预测。DunedinPACE是老年学和老年科学的一种新的衰老速度血液生物标志物。这项研究得到了美国国家老龄化研究所赠款AG 032282、AG 061378、AG 066887和英国医学研究理事会资助MR/P005918/1的支持。
Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome). We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets. DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge. DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience. This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.