INTRODUCTION Multifactorial biological processes underpin dysregulation over several individual physiological systems. However, it is challenging to characterize and model this multisystemic dysregulation and its relationship with individual physiologic systems. We operationalized a theory-driven measure of multisystem dysregulation and empirically tested for measurement differences by key characteristics. METHODS We used the Women's Health and Aging Studies (WHAS) I and II (N = 649), and the Health ABC study (N = 1515). Twelve biomarkers representing multiple systems including stress response (e.g., inflammation), endocrine system, and energy regulation were identified. A series of confirmatory factor analyses (CFA) were conducted to evaluate the interplay between physiological systems and underlying multisystem dysregulation. We evaluated convergent criterion validity of a score for multisystem dysregulation against the physical frailty phenotype, and predictive criterion validity with incidence of walking difficulty and mortality. RESULTS A bifactor CFA, a model in which dysregulation of individual systems proceeds independently of generalized dysregulation, fit data well in WHAS (RMSEA: 0.019; CFI: 0.977; TLI: 0.961) and Health ABC (RMSEA: 0.047; CFI: 0.874; TLI: 0.787). The general dysregulation factor was associated with frailty (OR: 2.2, 95 % CI: 1.4, 3.5), and elevated risk of incident walking difficulty and mortality. Findings were replicated in Health ABC. DISCUSSION Biomarker data from two epidemiologic studies support the construct of multisystem physiological dysregulation. Results further suggest system-specific and system-wide processes have unique and non-overlapping contributions to dysregulation in biological markers.

中文翻译：

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生理多系统失调测量的推导：来自 WHAS 和健康 ABC 的结果。

引言 多因素生物过程是几个个体生理系统失调的基础。然而，表征和模拟这种多系统失调及其与个体生理系统的关系具有挑战性。我们实施了多系统失调的理论驱动测量，并根据关键特征对测量差异进行了实证测试。方法 我们使用了女性健康与衰老研究 (WHAS) I 和 II (N = 649) 以及 Health ABC 研究 (N = 1515)。鉴定了代表多个系统的十二种生物标志物，包括应激反应（例如，炎症）、内分泌系统和能量调节。进行了一系列验证性因素分析 (CFA) 以评估生理系统和潜在的多系统失调之间的相互作用。我们评估了针对身体虚弱表型的多系统失调评分的收敛标准有效性，以及对行走困难和死亡率发生率的预测标准有效性。结果 双因素 CFA 是一种模型，其中个体系统的失调独立于广义失调进行，在 WHAS（RMSEA：0.019；CFI：0.977；TLI：0.961）和 Health ABC（RMSEA：0.047；CFI：0.874；TLI）中拟合数据良好: 0.787)。一般失调因素与虚弱（OR：2.2，95% CI：1.4，3.5）以及意外行走困难和死亡风险升高有关。结果在 Health ABC 中得到了复制。讨论 来自两项流行病学研究的生物标志物数据支持多系统生理失调的构建。