Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians and 1267 controls. Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. Further in silico analysis revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes-or genetic signatures-of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.

中文翻译：

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人类超长寿命的基因特征


健康老龄化被认为反映了环境因素（生活方式选择）和遗传因素的综合影响。为了探索遗传因素的影响，我们对 1055 名百岁老人和 1267 名对照者的超长寿命 (EL) 进行了全基因组关联研究。利用这些数据，我们建立了一个包含 150 个单核苷酸多态性 (SNP) 的遗传模型，发现它可以在一组独立的百岁老人和对照中以 77% 的准确率预测 EL。进一步的计算机分析显示，90% 的百岁老人可分为 19 个簇，这些簇的特征是具有不同预测价值的 SNP 基因型（或遗传特征）的不同组合。不同的特征证明了 EL 的遗传复杂性，与年龄相关疾病（例如痴呆、高血压和心血管疾病）的患病率和发病年龄的差异相关，可能有助于将这种复杂的表型分解为健康的亚表型。老化。