SIRT3基因（人类沉默信息调节因子Sir2同源物）的变异性与老年人的生存情况
Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly.
作者信息
Rose G, Dato S, Altomare K, Bellizzi D, Garasto S, Greco V, Passarino G, Feraco E, Mari V, Barbi C, BonaFe M, Franceschi C, Tan Q, Boiko S, Yashin A I, De Benedictis G
机构信息
Department of Cell Biology, University of Calabria, Rende 87030, Italy.
出版信息
Exp Gerontol. 2003 Oct;38(10):1065-70. doi: 10.1016/s0531-5565(03)00209-2.
The human sirtuin 3 (SIRT3) gene encodes a putative mitochondrial NAD-dependent deacetylase (SIRT3) which belongs to the evolutionary conserved family of sirtuin 2 proteins. Studies in model organisms have demonstrated that SIR2 genes control lifespan, while no data are available regarding a possible role of SIRT3 in human longevity. By analysing the genotype-specific survival function relevant to the G477T marker of SIRT3, we found that in males the TT genotype increases (p=0.0272), while the GT genotype decreases (p=0.0391) survival in the elderly. Since SIRT3 lies in a chromosomal region (11p15.5) where four genes potentially associated with longevity are located (HRAS1, Insulin-like Growth Factor 2, Proinsulin, and Tyrosine Hydroxylase) we tested for linkage-disequilibrium between G477T alleles and alleles of the above genes. The disequilibrium was not significant in any case, thus suggesting that SIRT3 itself, or a gene strictly linked to SIRT3, may have a role in human longevity.
人类沉默调节蛋白3（SIRT3）基因编码一种假定的线粒体烟酰胺腺嘌呤二核苷酸（NAD）依赖性脱乙酰酶（SIRT3），它属于进化上保守的沉默调节蛋白2家族。对模式生物的研究表明，SIR2基因控制寿命，但关于SIRT3在人类长寿中可能发挥的作用尚无数据。通过分析与SIRT3的G477T标记相关的基因型特异性生存函数，我们发现，在男性中，TT基因型会增加（p = 0.0272）老年人的生存率，而GT基因型则会降低（p = 0.0391）老年人的生存率。由于SIRT3位于一个染色体区域（11p15.5），该区域有四个可能与长寿相关的基因（HRAS1、胰岛素样生长因子2、胰岛素原和酪氨酸羟化酶），我们测试了G477T等位基因与上述基因的等位基因之间的连锁不平衡。在任何情况下，这种不平衡都不显著，因此表明SIRT3本身或与SIRT3紧密连锁的一个基因可能在人类长寿中发挥作用。
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