Erikson Galina A, Bodian Dale L, Rueda Manuel, Molparia Bhuvan, Scott Erick R, Scott-Van Zeeland Ashley A, Topol Sarah E, Wineinger Nathan E, Niederhuber John E, Topol Eric J, Torkamani Ali
The Scripps Translational Science Institute, Scripps Health, and The Scripps Research Institute, La Jolla, CA 92037, USA.
Inova Translational Medicine Institute, Inova Health System, Falls Church, VA 22042 USA.
Cell. 2016 May 5;165(4):1002-11. doi: 10.1016/j.cell.2016.03.022. Epub 2016 Apr 21.
Studies of long-lived individuals have revealed few genetic mechanisms for protection against age-associated disease. Therefore, we pursued genome sequencing of a related phenotype-healthy aging-to understand the genetics of disease-free aging without medical intervention. In contrast with studies of exceptional longevity, usually focused on centenarians, healthy aging is not associated with known longevity variants, but is associated with reduced genetic susceptibility to Alzheimer and coronary artery disease. Additionally, healthy aging is not associated with a decreased rate of rare pathogenic variants, potentially indicating the presence of disease-resistance factors. In keeping with this possibility, we identify suggestive common and rare variant genetic associations implying that protection against cognitive decline is a genetic component of healthy aging. These findings, based on a relatively small cohort, require independent replication. Overall, our results suggest healthy aging is an overlapping but distinct phenotype from exceptional longevity that may be enriched with disease-protective genetic factors. VIDEO ABSTRACT.
对长寿个体的研究揭示了很少有抵御与年龄相关疾病的遗传机制。因此,我们对一种相关表型——健康衰老进行了基因组测序,以了解在无医学干预情况下无病衰老的遗传学机制。与通常聚焦于百岁老人的超长寿命研究不同,健康衰老与已知的长寿变异无关,但与对阿尔茨海默病和冠状动脉疾病的遗传易感性降低有关。此外,健康衰老与罕见致病变异率的降低无关,这可能表明存在抗病因素。与此可能性相符的是,我们识别出了提示性的常见和罕见变异遗传关联,这意味着抵御认知衰退是健康衰老的一个遗传组成部分。这些基于相对较小队列的发现需要独立验证。总体而言,我们的结果表明健康衰老是一种与超长寿命重叠但又不同的表型,可能富含疾病保护遗传因素。视频摘要。