Genetics of aging, health, and survival: dynamic regulation of human longevity related traits.
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2015
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Abstract
BACKGROUND: The roles of genetic factors in human longevity would be better understood if one can use more efficient methods in genetic analyses and investigate pleiotropic effects of genetic variants on aging and health related traits. DATA AND METHODS: We used EMMAX software with modified correction for population stratification to perform genome wide association studies (GWAS) of female lifespan from the original FHS cohort. The male data from the original FHS cohort and male and female data combined from the offspring FHS cohort were used to confirm findings. We evaluated pleiotropic effects of selected genetic variants as well as gene-smoking interactions on health and aging related traits. Then we reviewed current knowledge on functional properties of genes related to detected variants. RESULTS: The eight SNPs with genome-wide significant variants were negatively associated with lifespan in both males and females. After additional QC, two of these variants were selected for further analyses of their associations with major diseases (cancer and CHD) and physiological aging changes. Gene-smoking interactions contributed to these effects. Genes closest to detected variants appear to be involved in similar biological processes and health disorders, as those found in other studies of aging and longevity e.g., in cancer and neurodegeneration. CONCLUSIONS: The impact of genes on longevity may involve trade-off-like effects on different health traits. Genes that influence lifespan represent various molecular functions but may be involved in similar biological processes and health disorders, which could contribute to genetic heterogeneity of longevity and the lack of replication in genetic association studies.
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Yashin, Anatoliy I, Deqing Wu, Liubov S Arbeeva, Konstantin G Arbeev, Alexander M Kulminski, Igor Akushevich, Mikhail Kovtun, Irina Culminskaya, et al. (2015). Genetics of aging, health, and survival: dynamic regulation of human longevity related traits. Front Genet, 6. p. 122. 10.3389/fgene.2015.00122 Retrieved from https://hdl.handle.net/10161/14821.
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Scholars@Duke
Anatoli I. Yashin
Dequing Wu
Konstantin Arbeev
Konstantin G. Arbeev received the M.S. degree in Applied Mathematics from Moscow State University (branch in Ulyanovsk, Russia) in 1995 and the Ph.D. degree in Mathematics and Physics (specialization in Theoretical Foundations of Mathematical Modeling, Numerical Methods and Programming) from Ulyanovsk State University (Russia) in 1999. He was a post-doctoral fellow in Max Planck Institute for Demographic Research in Rostock (Germany) before moving to Duke University in 2004 to work as a Research Scientist and a Senior Research Scientist in the Department of Sociology and the Social Science Research Institute (SSRI). He is currently an Associate Research Professor in SSRI. Dr. Arbeev's major research interests are related to three interconnected fields of biodemography, biostatistics and genetic epidemiology as pertains to research on aging. The focus of his research is on discovering genetic and non-genetic factors that can affect the process of aging and determine longevity and healthy lifespan. He is interested in both methodological advances in this research area as well as their practical applications to analyses of large-scale longitudinal studies with phenotypic, genetic and, recently, genomic information. Dr. Arbeev authored and co-authored more than 150 peer-reviewed publications in these areas.
Alexander Kulminski
Igor Akushevich
Svetlana Ukraintseva
Dr. Ukraintseva studies the causes of human aging and the associated decline in whole-body resilience, with the goal of identifying genetic and other factors that drive this decline and contribute to the age-related increase in all-cause mortality risk, ultimately limiting longevity even in individuals without major diseases. She also investigates the “multi-hit” mechanism of Alzheimer’s disease and the complex, including trade‑off–like, relationships between Alzheimer’s disease and cancer. She actively explores the role of infectious diseases and compromised immunity in Alzheimer’s development, as well as the interplay between vaccines and genetic factors, to advance personalized vaccine repurposing for AD prevention. To address these questions, Dr. Ukraintseva and her team analyze large human datasets containing comprehensive information on millions of individuals. She is a PI and key investigator on several NIH-funded grants and has authored more than 150 peer‑reviewed publications, including in major journals such as JAMA, Nature group journals, Stroke, Alzheimer’s & Dementia, and others.
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