title: Beta2-adrenergic receptor gene polymorphisms as systemic determinants of healthy aging in an evolutionary context.
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.
authors.affiliation: Center for Population Health and Aging, Duke University Population Research Institute, Durham, NC 27708, USA. ander.Kulminski@duke.edu
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Kulminski
authors.forename: Irina
authors.initials: I
authors.lastname: Culminskaya
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Ukraintseva
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Arbeev
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Land
authors.forename: Anatoli I
authors.initials: AI
authors.lastname: Yashin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D002318:Cardiovascular Diseases / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D019143:Evolution, Molecular; D005260:Female; D006262:Health; D006801:Humans; D008136:Longevity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012306:Risk; D055815:Young Adult
chemical_list: D018343:Receptors, Adrenergic, beta-2
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