科學(xué)家發(fā)現(xiàn)了一個稱為FOXO3A的基因與人類的健康和長壽有強烈的相關(guān)性,。此前,,只有1個基因被發(fā)現(xiàn)和人類長壽相關(guān),那就是營養(yǎng)運輸分子ApoE的基因,。
對動物衰老模型的研究已經(jīng)發(fā)現(xiàn)了幾個胰島素信號傳導(dǎo)路徑的組成部分,,例如人體的感知胰島素的FOXO蛋白。Bradley Willcox及其同事研究了一群定期接受健康檢查的日裔美國男性,。這組科學(xué)家篩查了受試者的DNA,,把重點放在胰島素路徑的5個基因上。他們計算了每個基因的三個位置上出現(xiàn)的DNA堿基如何與一個綜合健康標準集相關(guān),。
FOXO3A基因上的一個位置特別突出,。在組成了DNA的4種堿基(A、T,、C,、G)中,大多數(shù)受試者在一對染色體的這個位置上擁有的是胸腺嘧啶(T),。但是鳥嘌呤(G)取代了T的受試者在當初健康檢查的時候的健康狀況更好,。20年后,在最終到達了98歲平均年齡的男性組中G出現(xiàn)的頻率更高,。這組科學(xué)家在這些老年人中的許多人身上發(fā)現(xiàn)了有兩個G(GG)的等位基因,,他們認為這可能是這些人在老齡時非常健康的原因。(生物谷Bioon.com)
生物谷推薦原始出處:
PNAS published September 2, 2008, doi:10.1073/pnas.0801030105
FOXO3A genotype is strongly associated with human longevity
Bradley J. Willcox, Timothy A. Donlon, Qimei He, Randi Chen, John S. Grove, Katsuhiko Yano, Kamal H. Masaki, D. Craig Willcox, Beatriz Rodriguez, and J. David Curb
Human longevity is a complex phenotype with a significant familial component, yet little is known about its genetic antecedents. Increasing evidence from animal models suggests that the insulin/IGF-1 signaling (IIS) pathway is an important, evolutionarily conserved biological pathway that influences aging and longevity. However, to date human data have been scarce. Studies have been hampered by small sample sizes, lack of precise phenotyping, and population stratification, among other challenges. Therefore, to more precisely assess potential genetic contributions to human longevity from genes linked to IIS signaling, we chose a large, homogeneous, long-lived population of men well-characterized for aging phenotypes, and we performed a nested-case control study of 5 candidate longevity genes. Genetic variation within the FOXO3A gene was strongly associated with human longevity. The OR for homozygous minor vs. homozygous major alleles between the cases and controls was 2.75 (P = 0.00009; adjusted P = 0.00135). Long-lived men also presented several additional phenotypes linked to healthy aging, including lower prevalence of cancer and cardiovascular disease, better self-reported health, and high physical and cognitive function, despite significantly older ages than controls. Several of these aging phenotypes were associated with FOXO3A genotype. Long-lived men also exhibited several biological markers indicative of greater insulin sensitivity and this was associated with homozygosity for the FOXO3A GG genotype. Further exploration of the FOXO3A gene, human longevity and other aging phenotypes is warranted in other populations