Trajectories of physiological dysregulation predicts mortality and health outcomes in a consistent manner across three populations.

Abstract

Mechanistic and evolutionary perspectives both agree that aging involves multiple integrated biochemical networks in the organism. In particular, the homeostatic physiological dysregulation (PD) hypothesis contends that aging is caused by the progressive breakdown of key regulatory processes. However, nothing is yet known about the specifics of how PD changes with age and affects health. Using a recently validated measure of PD involving the calculation of a multivariate distance (DM) from biomarker data, we show that PD trajectories predict mortality, frailty, and chronic diseases (cancer, cardiovascular diseases, and diabetes). Specifically, relative risks of outcomes associated with individual slopes in (i.e. rate of) dysregulation range 1.20-1.40 per unit slope. We confirm the results by replicating the analysis using two suites of biomarkers selected with markedly different criteria and, for mortality, in three longitudinal cohort-based studies. Overall, the consistence of effect sizes (direction and magnitude) across data sets, biomarker suites and outcomes suggests that the positive relationship between DM and health outcomes is a general phenomenon found across human populations. Therefore, the study of dysregulation trajectories should allow important insights into aging physiology and provide clinically meaningful predictors of outcomes.

• Authors: Emmanuel Milot, V Morissette-Thomas, Qing Li, Linda P Fried, Luigi Ferrucci, Alan A Cohen
• Journal: Mechanisms of ageing and development (Mech Ageing Dev) 2014 Nov-Dec Vol. 141-142 Pg. 56-63 ISSN: 1872-6216 [Electronic] Ireland
• PMID: 25454986 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Topics

• Adult
• Aged
• Aged, 80 and over
• Aging
• Cardiovascular Diseases (mortality)
• Chronic Disease
• Diabetes Mellitus (mortality)
• Female
• Humans
• Longitudinal Studies
• Male
• Middle Aged
• Neoplasms (mortality)