title: Association analyses of insulin signaling pathway gene polymorphisms with healthy aging and longevity in Americans of Japanese ancestry.
abstract: Evidence from model organisms suggests that the insulin/IGF-1 signaling pathway has an important, evolutionarily conserved influence over rate of aging and thus longevity. In humans, the FOXO3 gene is the only widely replicated insulin/IGF-1 signaling pathway gene associated with longevity across multiple populations. Therefore, we conducted a nested case-control study of other insulin/IGF-1 signaling genes and longevity, utilizing a large, homogeneous, long-lived population of American men of Japanese ancestry, well characterized for aging phenotypes. Genotyping was performed of single nucleotide polymorphisms, tagging most of the genetic variation across several genes in the insulin/IGF-1 signaling pathway or related gene networks that may be influenced by FOXO3, namely, ATF4, CBL, CDKN2, EXO1, and JUN. Two initial, marginal associations with longevity did not remain significant after correction for multiple comparisons, nor were they correlated with aging-related phenotypes.
authors.affiliation: DSc Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, 347 North Kuakini Street, HPM-9, Honolulu, Hawaii 96817. brian.morris@sydney.edu.au.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Morris
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Donlon
authors.forename: Qimei
authors.initials: Q
authors.lastname: He
authors.forename: John S
authors.initials: JS
authors.lastname: Grove
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.forename: Ayako
authors.initials: A
authors.lastname: Elliott
authors.forename: D Craig
authors.initials: DC
authors.lastname: Willcox
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Willcox
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001213:Asian / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D045643:DNA Repair Enzymes / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000235:genetics; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics; D005787:Gene Frequency; D016758:Genes, jun / Q000235:genetics; D019942:Genes, p16 / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007564:Japan / Q000208:ethnology; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*
chemical_list: C497109:ATF4 protein, human; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D007328:Insulin; D051701:Activating Transcription Factor 4; D007334:Insulin-Like Growth Factor I; D050721:Proto-Oncogene Proteins c-cbl; C114331:EXO1 protein, human; D005090:Exodeoxyribonucleases; C067419:CBL protein, human; D045643:DNA Repair Enzymes
keywords: Human.; Insulin signaling genes; Longevity; Molecular genetics