Garatachea Nuria, Fuku Noriyuki, He Zi-Hong, Tian Ye, Arai Yasumichi, Abe Yukiko, Murakami Haruka, Miyachi Motohiko, Yvert Thomas, Venturini Letizia, Santiago Catalina, Santos-Lozano Alejandro, Rodríguez Gabriel, Ricevuti Giovanni, Pareja-Galeano Helios, Sanchis-Gomar Fabian, Emanuele Enzo, Hirose Nobuyoshi, Lucia Alejandro
1 Faculty of Health and Sport Science, University of Zaragoza , Huesca, Spain .
Rejuvenation Res. 2014 Oct;17(5):430-8. doi: 10.1089/rej.2014.1570.
Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100-111 years, 144 women) and healthy controls (n=355, 20-50 years, 284 women); (2) Italian centenarians (n=79, 100-104 years, 40 women) and controls (n=316, 29-50 years, 156 women); and (3) Japanese centenarians (n=742, 100-116 years, 623 women) and healthy controls (n=499, 23-59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging.
粘着斑对细胞存活至关重要。粘着斑激酶（FAK，即PTK2）是人类相互作用组的重要组成部分，因此是一种潜在的与长寿相关的蛋白质。在此，我们研究了PTK2基因的两个单核苷酸多态性（SNP）（rs7843014、rs7460）与超长寿命（EL）之间的关联。除了通过测定荧光素酶基因报告活性来深入了解它们的功能外，我们还研究了这两个SNP在三个不同队列中的基因型/等位基因频率：（1）西班牙百岁老人（n = 175，年龄100 - 111岁，女性144名）和健康对照（n = 355，年龄20 - 50岁，女性284名）；（2）意大利百岁老人（n = 79，年龄100 - 104岁，女性40名）和对照（n = 316，年龄29 - 50岁，女性156名）；以及（3）日本百岁老人（n = 742，年龄100 - 116岁，女性623名）和健康对照（n = 499，年龄23 - 59岁，女性356名）。两个SNP均具有功能意义，与其他等位基因相比，A等位基因上调荧光素酶活性（分别为rs7460的T等位基因和rs7843014的C等位基因）。在西班牙队列中，两个SNP的A等位基因均与EL呈负相关（rs7460，经性别调整的优势比[OR] = 0.40，95%置信区间[CI] 0.3，0.6，p < 0.001）；rs7843014，OR = 0.37，95% CI 0.3，0.5，p < 0.001）。具有rs7460 - TT基因型成为百岁老人的OR为6.68（95% CI 4.1，10.8，p < 0.001）。rs7843014的CC基因型也与EL呈正相关（OR = 7.58，95% CI 4.6，12.3，p < 0.001）。然而，在意大利或日本队列中未发现关联。因此，FAK基因的两种基因型，rs7460 TT和rs7843014 CC，可能与较低的基因表达相关，并可能有利于西班牙人群达到超长寿命。需要进一步研究以揭示FAK表达可能影响衰老速率的机制。
