Resistance to stresses and reliability of biological systems: Insights for genetic studies of human aging, health, and longevity

Abstract

© 2016 IEEE.Connection between stress resistance and longevity in biological organisms is widely discussed and confirmed experimentally. Much less is known about the roles of genetic and non-genetic factors in regulation of such connection. Earlier studies emphasized that mechanism that realizes such connection involves interplay between processes of individual aging and external challenges. As a result of such interplay the parameters of the Gompertz mortality curve are negatively correlated. Such correlation has been also observed in the process of survival improvement in developed part of the world during the first part of the last century. The mortality decline was mainly due to favorable changes in external and living conditions as well as progress in health care. Surprisingly, similar pattern of survival changes is observed in the groups of individuals ranked with respect to the number of «longevity» alleles carried by individuals. We showed that this phenomenon can be interpreted as an increase in resistance to stresses and showed that similar effect is observed in reliability of technical systems when redundancy of their components increases. The availability of longitudinal data for genotyped individuals opens unique opportunity to address more sophisticated questions about roles of genetic and non-genetic factors in connection between aging, stress resistance and longevity in humans. For this purpose the dynamic model of human mortality and aging is used. We show how such model can be used in genetic analyses of fundamental processes of interaction between genetic and non-genetic factors to influence human longevity.

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10.1109/SMRLO.2016.70

Scholars@Duke

Wu

Dequing Wu

Research Scientist, Senior
Akushevich

Igor Akushevich

Research Professor in the Social Science Research Institute
Kulminski

Alexander Kulminski

Research Professor in the Social Science Research Institute
Kovtun

Mikhail Kovtun

Biostatistician III
Zhbannikov

Ilya Zhbannikov

Biostatistician III
Ukraintseva

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.


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