Association analyses of insulin signaling pathway gene polymorphisms with healthy aging and longevity in Americans of Japanese ancestry.

Authors: Morris BJ; Donlon TA; He Q; Grove JS; Masaki KH; Elliott A; Willcox DC; Willcox BJ

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.

Keywords: Activating Transcription Factor 4/genetics; Aged, 80 and over; Aging/*genetics; Asian Americans/*genetics; Case-Control Studies; Cohort Studies; DNA Repair Enzymes/genetics; Exodeoxyribonucleases/genetics; Forkhead Transcription Factors/genetics; Gene Frequency; Genes, jun/genetics; Genes, p16/physiology; Genetic Variation/genetics; Genotype; Humans; Insulin/*genetics; Insulin Resistance/genetics; Insulin-Like Growth Factor I/genetics; Japan/ethnology; Longevity/*genetics; Longitudinal Studies; Male; Polymorphism, Genetic/*genetics; Polymorphism, Single Nucleotide/genetics; Proto-Oncogene Proteins c-cbl/genetics; Signal Transduction/*genetics
Journal: The journals of gerontology. Series A, Biological sciences and medical sciences
Volume: 69
Issue: 3
Pages: 270-3
Date: June 19, 2013
PMID: 23770741
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Citation:

Morris BJ, Donlon TA, He Q, Grove JS, Masaki KH, Elliott A, Willcox DC, Willcox BJ (2014) Association analyses of insulin signaling pathway gene polymorphisms with healthy aging and longevity in Americans of Japanese ancestry. The journals of gerontology. Series A, Biological sciences and medical sciences 69: 270-3.


Longevity Variant Associations (p-value):
  • rs1048310 (0.87)
  • rs6519194 (0.41)
  • rs738288 (0.54)
  • rs6589722 (0.015)
  • rs12786104 (0.12)
  • rs11217184 (0.8)
  • rs2249466 (0.9)
  • rs7914 (0.69)
  • rs2511837 (0.14)
  • rs10811661 (0.13)
  • rs1776180 (0.16)
  • rs2999131 (0.31)
  • rs1815274 (0.18)
  • rs17356414 (0.082)
  • rs1853432 (0.52)

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