DSc Honolulu Heart Program (HHP)/Honolulu-Asia Aging Study (HAAS), Kuakini Medical Center, 347 North Kuakini Street, HPM-9, Honolulu, Hawaii 96817.
J Gerontol A Biol Sci Med Sci. 2014 Mar;69(3):270-3. doi: 10.1093/gerona/glt082. Epub 2013 Jun 14.
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.
来自模式生物的证据表明，胰岛素/IGF-1 信号通路对衰老速度和寿命有着重要的、进化上保守的影响。在人类中，FOXO3 基因是唯一广泛复制的与多个人群的长寿相关的胰岛素/IGF-1 信号通路基因。因此，我们利用一个具有很大、同质、长寿的美国日本裔男性人群，对其他胰岛素/IGF-1 信号基因与长寿进行了嵌套病例对照研究，这些人群对衰老表型进行了很好的特征描述。对单核苷酸多态性进行了基因分型，这些多态性标记了胰岛素/IGF-1 信号通路或可能受 FOXO3 影响的相关基因网络中的几个基因的大部分遗传变异，这些基因包括 ATF4、CBL、CDKN2、EXO1 和 JUN。在进行多次比较校正后，最初与长寿相关的两个边缘关联不再显著，也与与衰老相关的表型无关。
