The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006–2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M chip) followed by imputation was conducted. Visit 2 (2014–2017) repeated all Visit 1 protocols and added carotid ultrasonography of atherosclerotic plaque and wall thickness, additional cognitive testing, and perceived fatigability. On average, LLFS families show healthier aging profiles than reference populations, such as the Framingham Heart Study, at all age/sex groups, for many critical healthy aging phenotypes. However, participants are not uniformly protected. There is considerable heterogeneity among the pedigrees, with some showing exceptional cognition, others showing exceptional grip strength, others exceptional pulmonary function, etc. with little overlap in these families. There is strong heritability for key healthy aging phenotypes, both cross-sectionally and longitudinally, suggesting that at least some of this protection may be genetic. Little of the variance in these heritable phenotypes is explained by the common genome (GWAS + Imputation), which may indicate that rare protective variants for specific phenotypes may be running in selected families.

中文翻译：

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NIA 长寿家族研究：横截面和纵向表型的目标、设计和遗传力

NIA 长寿家庭研究 (LLFS) 是一项纵向、多中心、多国、基于人群的多代家庭研究，研究长寿和健康老龄化的遗传和非遗传决定因素。访问 1 面对面评估（2006-2009 年）从 539 个两代家庭中招募了 4 953 名个体，这些个体选自家庭长寿选择评分（FLoSS，它量化了长寿的家族聚集程度）的上 1% 尾部。收集人口统计学、人体测量学、认知、日常生活活动、踝臂指数、血压、身体机能和肺功能，以及血清、血浆、淋巴细胞、红细胞和 DNA。进行全基因组关联扫描 (GWAS) (Ilumina Omni 2.5M 芯片)，然后进行插补。第 2 次访问（2014-2017 年）重复了第 1 次访问的所有方案，并增加了动脉粥样硬化斑块和壁厚的颈动脉超声检查、额外的认知测试和感知疲劳性。平均而言，对于许多关键的健康衰老表型，LLFS 家族在所有年龄/性别组中都显示出比参考人群更健康的衰老特征，例如弗雷明汉心脏研究。但是，参与者并没有得到统一的保护。家系之间存在相当大的异质性，其中一些表现出非凡的认知能力，另一些表现出非凡的握力，另一些表现出非凡的肺功能等，这些家族几乎没有重叠。关键的健康衰老表型在横截面和纵向上都具有很强的遗传性，这表明至少有一些这种保护可能是遗传的。