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Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

ABSTRACT: While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently developed measure of physiological dysregulation based on the statistical distance of biomarker profiles in the framework of the stochastic process model of aging, using data on blood pressure, heart rate, cholesterol, glucose, hematocrit, body mass index, and mortality in the Framingham original cohort. This allowed us to evaluate how physiological dysregulation is related to different aging-related characteristics such as decline in stress resistance and adaptive capacity (which typically are not observed in the data and thus can be analyzed only indirectly), and, ultimately, to estimate how such dynamic relationships increase mortality risk with age. We found that physiological dysregulation increases with age; that increased dysregulation is associated with increased mortality, and increasingly so with age; and that, in most but not all cases, there is a decreasing ability to return quickly to baseline physiological state with age. We also revealed substantial sex differences in these processes, with women becoming dysregulated more quickly but with men showing a much greater sensitivity to dysregulation in terms of mortality risk.

SUBMITTER: Arbeev KG

PROVIDER: S-EPMC4725219 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

Arbeev Konstantin G KG Cohen Alan A AA Arbeeva Liubov S LS Milot Emmanuel E Stallard Eric E Kulminski Alexander M AM Akushevich Igor I Ukraintseva Svetlana V SV Christensen Kaare K Yashin Anatoliy I AI

Frontiers in public health 20160125

While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently developed measure of physiological dysregulation based on the statistical distance of biomarker profiles in the framework of the stochastic process model of aging, using data on blood pressure, heart rate, cholesterol, glucose, hematocrit, body mass ...[more]

PMID: 26835445

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Project description:BackgroundPhysical activity (PA) is a recognized contributor to healthy aging. However, the majority of studies exploring its associations with adverse outcomes in cohorts of older adults use single-time PA estimates, which do not consider its dynamic nature. The aim of the present study is to explore the presence of different PA trajectories in the Toledo Study of Healthy Aging and their association with adverse outcomes. Our hypothesis is that prospectively maintaining or increasing PA is associated with a reduced risk of adverse outcomes.MethodsWe used data from 1679 participants enrolled in the Toledo Study of Healthy Aging. Trajectories based on the Physical Activity Scale for the Elderly were identified using group-based trajectory modelling. Cox and logistic regression were used to investigate associations between PA trajectories and mortality and hospitalization, and incident and worsening disability, respectively. Mortality was ascertained by linkage to the Spanish National Death Index; disability was evaluated through the Katz Index; and hospitalization was defined as the first admission to Toledo Hospital. Models were adjusted by age, sex, smoking, Charlson Index, education, cognitive impairment, polypharmacy, and Katz Index at Wave 2.ResultsWe found four PA-decreasing and one PA-increasing trajectories: high PA-consistent (n = 566), moderate PA-mildly decreasing (n = 392), low PA-increasing (n = 237), moderate PA-consistent (n = 191), and low PA-decreasing (n = 293). Belonging to the high PA-consistent trajectory group was associated with reduced risks of mortality as compared with the low PA-decreasing group [hazard ratio (HR) 1.68; 95% confidence interval (CI) = 1.21-2.31] and hospitalization compared with the low PA-increasing and low PA-decreasing trajectory groups (HR 1.24; 95% CI = 1.004-1.54 and HR 1.25; 95% CI = 1.01-1.55, respectively) and with lower rates of incident [odds ratio (OR) 3.14; 95% CI = 1.59-6.19] and worsening disability (OR 2.16; 95% CI = 1.35-3.45) in relation to the low PA-decreasing trajectory group and at follow-up. Increasing PA during late life (low PA-increasing group) was associated with lower incident disability rates (OR 0.38; 95% CI = 0.19-0.82) compared with decreasing PA (low PA-decreasing group), despite similar baseline PA.ConclusionsOur results suggest that sustaining higher PA levels during aging might lead to healthy aging, characterized by a reduction in adverse outcomes. Our study supports the need for enhancing PA participation among older populations, with the goal of reducing personal and economic burden in a worldwide aging population.

Dataset Information

Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

Publications

Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk.

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