Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context.
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2010-05
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Abstract
The Gln(27)Glu polymorphism but not the Arg(16)Gly polymorphism of the beta2-adrenergic receptor (ADRB2) gene appears to be associated with a broad range of aging-associated phenotypes, including cancers at different sites, myocardial infarction (MI), intermittent claudication (IC), and overall/healthy longevity in the Framingham Heart Study Offspring cohort. The Gln(27)Gln genotype increases risks of cancer, MI and IC, whereas the Glu(27) allele or, equivalently, the Gly(16)Glu(27) haplotype tends to be protective against these diseases. Genetic associations with longevity are of opposite nature at young-old and oldest-old ages highlighting the phenomenon of antagonistic pleiotropy. The mechanism of antagonistic pleiotropy is associated with an evolutionary-driven advantage of carriers of a derived Gln(27) allele at younger ages and their survival disadvantage at older ages as a result of increased risks of cancer, MI and IC. The ADRB2 gene can play an important systemic role in healthy aging in evolutionary context that warrants exploration in other populations.
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Kulminski, Alexander M, Irina Culminskaya, Svetlana V Ukraintseva, Konstantin G Arbeev, Kenneth C Land and Anatoli I Yashin (2010). Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context. Mech Ageing Dev, 131(5). pp. 338–345. 10.1016/j.mad.2010.04.001 Retrieved from https://hdl.handle.net/10161/14883.
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Scholars@Duke
Alexander Kulminski
Irina Kulminskaya
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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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.
Kenneth C. Land
I received my Ph.D. in sociology and mathematics from the University of Texas at Austin in 1969. After a year of postdoctoral study in mathematical statistics at Columbia University in New York City, I taught there and was a member of the staff of the Russell Sage Foundation for three years. I then was successively a member of the faculties of the University of Illinois at Urbana Champaign and the University of Texas at Austin before joining the Duke Sociology Department as Chairman in 1986. I served as Chair of Sociology from January 1986 to August 1997. My main research interests are contemporary social trends and quality-of-life measurement, social problems, demography, criminology, organizations, and mathematical and statistical models and methods for the study of social and demographic processes. I have done extensive research in each of these areas and have been elected a Fellow of the American Statistical Association (1978), the Sociological Research Association (1981), the American Association for the Advancement of Science (1992), the International Society for Quality-of-Life Studies (1997), and the American Society of Criminology (2004). I teach Contemporary Social Problems (SOCIOL 111), Advanced Methods of Demographic Analysis, and the Demography of Aging Proseminar (SOCIOL 750S). My other interests include tennis, jogging (10 kilometers), and music.
Anatoli I. Yashin
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