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


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.





Published Version (Please cite this version)


Publication Info

Arbeev, Konstantin G, Alan A Cohen, Liubov S Arbeeva, Emmanuel Milot, Eric Stallard, Alexander M Kulminski, Igor Akushevich, Svetlana V Ukraintseva, et al. (2016). Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk. Front Public Health, 4. p. 3. 10.3389/fpubh.2016.00003 Retrieved from https://hdl.handle.net/10161/14757.

This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.



Alexander Kulminski

Research Professor in the Social Science Research Institute

Svetlana Ukraintseva

Research Professor in the Social Science Research Institute

Dr. Ukraintseva studies causes of human aging and related decline in resilience, to identify genetic and other factors responsible for the increase in mortality risk with age eventually limiting longevity. She explores complex relationships, including trade-offs, between physiological aging-changes and risks of major diseases (with emphasis on Alzheimer’s and cancer), as well as survival, to find new genetic and other targets for anti-aging interventions and disease prevention. She also investigates possibilities of repurposing of existing vaccines and treatments for AD prevention and interventions into the aging. For this, Dr. Ukraintseva and her team use data from several large human studies containing rich genetic and phenotypic information (including longitudinal measurements) on thousands of individuals. Dr. Ukraintseva is a PI and Key Investigator on several NIH funded grants, and has more than 130 peer-reviewed publications, including in major journals such as Nature Reviews, Stroke, European Journal of Human Genetics, and some other.


Anatoli I. Yashin

Research Professor in the Social Science Research Institute

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.