Tulane Center for Aging and Department of Medicine, Tulane University Health Sciences Center, Box 8513, 1430 Tulane Ave., New Orleans, 70112, LA, USA.
Department of Global Biostatistics and Data Science, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA, USA.
Geroscience. 2017 Feb;39(1):83-92. doi: 10.1007/s11357-017-9960-3. Epub 2017 Jan 14.
The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI over DNA methylation age measures was apparent when FI and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI remained significant but the DNA methylation measures did not. These results indicate that FI is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.
与实际年龄相比，生物年龄的衡量对于研究导致个体在衰老过程中健康和功能能力下降的异质性因素非常重要。已经提出了各种衡量生物衰老的方法。基于不同身体系统健康缺陷的虚弱指数得到了很好的研究，我们已经记录了使用由 34 个健康项目组成的虚弱指数 (FI) 来衡量生物年龄。另一种方法基于白细胞 DNA 甲基化。它被称为 DNA 甲基化年龄，该指标的衍生指标，如年龄加速差异和年龄加速残余，也已被采用。任何有用的生物年龄衡量标准都必须比实际年龄更好地预测生存率。荟萃分析表明，年龄加速差异和年龄加速残余是死亡率的重要预测指标，这使它们成为生物年龄的指标。在本文中，我们将基于 DNA 甲基化的测量方法与 FI 进行了比较。使用一个经过充分研究的队列，我们并排评估了这些方法在预测死亡率方面的效率。在存在实际年龄作为协变量的情况下，FI 是死亡率的显著预测因素，而基于 DNA 甲基化年龄的任何指标都不是。当 FI 和每个 DNA 甲基化年龄指标与实际年龄一起作为解释变量使用时，FI 的表现优于 DNA 甲基化年龄指标：FI 仍然显著，而 DNA 甲基化指标则不显著。这些结果表明，FI 是生物年龄的一个稳健预测指标，而这些 DNA 甲基化指标在很大程度上只是实际时间流逝的统计反映。
