Center for Clinical Big Data and Analytics, Second Affiliated Hospital and Department of Big Data in Health Science, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
J Gerontol A Biol Sci Med Sci. 2021 Aug 13;76(9):1627-1632. doi: 10.1093/gerona/glaa238.
This study aimed to: (i) develop 2 composite aging measures in the Chinese population using 2 recent advanced algorithms (the Klemera and Doubal method and Mahalanobis distance); and (ii) validate the 2 measures by examining their associations with mortality and disease counts.
Based on data from the China Nutrition and Health Survey (CHNS) 2009 wave (N = 8119, aged 20-79 years, 53.5% women), a nationwide prospective cohort study of the Chinese population, we developed Klemera and Doubal method-biological age (KDM-BA) and physiological dysregulation (PD, derived from Mahalanobis distance) using 12 biomarkers. For the validation analysis, we used Cox proportional hazard regression models (for mortality) and linear, Poisson, and logistic regression models (for disease counts) to examine the associations. We replicated the validation analysis in the China Health and Retirement Longitudinal Study (CHARLS, N = 9304, aged 45-99 years, 53.4% women).
Both aging measures were predictive of mortality after accounting for age and gender (KDM-BA, per 1-year, hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.08, 1.19; PD, per 1-SD, HR = 1.50, 95% CI = 1.33, 1.69). With few exceptions, these mortality predictions were robust across stratifications by age, gender, education, and health behaviors. The 2 aging measures were associated with disease counts both cross-sectionally and longitudinally. These results were generally replicable in CHARLS although 4 biomarkers were not available.
We successfully developed and validated 2 composite aging measures-KDM-BA and PD, which have great potentials for applications in early identifications and preventions of aging and aging-related diseases in China.
本研究旨在:(i)使用两种最新的先进算法(Klemera 和 Doubal 方法以及马氏距离),在中国人群中开发 2 种综合衰老指标;(ii)通过检查与死亡率和疾病计数的关联来验证这 2 种指标。
基于中国营养与健康调查(CHNS)2009 年(N=8119,年龄 20-79 岁,53.5%女性)的数据,我们对中国人群进行了一项全国性前瞻性队列研究,利用 12 种生物标志物开发了 Klemera 和 Doubal 方法生物学年龄(KDM-BA)和生理失调(PD,源自马氏距离)。为了验证分析,我们使用 Cox 比例风险回归模型(用于死亡率)和线性、泊松和逻辑回归模型(用于疾病计数)来检查关联。我们在 CHARLS(中国健康与退休纵向研究)中复制了验证分析(N=9304,年龄 45-99 岁,53.4%女性)。
在考虑年龄和性别后,这两种衰老指标都可以预测死亡率(KDM-BA,每增加 1 年,风险比 [HR] = 1.14,95%置信区间 [CI] = 1.08,1.19;PD,每增加 1 个标准差,HR = 1.50,95%CI = 1.33,1.69)。除了少数例外情况,这些死亡率预测在按年龄、性别、教育程度和健康行为分层时具有稳健性。这两种衰老指标在横断面和纵向都与疾病计数相关。这些结果在 CHARLS 中基本具有可重复性,尽管有 4 种生物标志物不可用。
我们成功地开发和验证了 2 种综合衰老指标-KDM-BA 和 PD,它们在中国早期识别和预防衰老和与衰老相关的疾病方面具有很大的应用潜力。