Healthy metabolic measures in humans are associated with longevity. Dysregulation leads to metabolic syndrome (MetS) and negative health outcomes. Recent exceptional longevity (EL) genome wide association studies have facilitated estimation of an individual’s polygenic risk score (PRS) for EL. We tested the hypothesis that individuals with high ELPRS have a low prevalence of MetS. Participants were from five cohorts of middle-aged to older adults. The primary analyses were performed in the UK Biobank (UKBB) (n = 407,800, 40–69 years). Replication analyses were undertaken using three Australian studies: Hunter Community Study (n = 2122, 55–85 years), Older Australian Twins Study (n = 539, 65–90 years) and Sydney Memory and Ageing Study (n = 925, 70–90 years), as well as the Swedish Gothenburg H70 Birth Cohort Studies (n = 2273, 70–93 years). MetS was defined using established criteria. Regressions and meta-analyses were performed with the ELPRS and MetS and its components. Generally, MetS prevalence (22–30%) was higher in the older cohorts. In the UKBB, high EL polygenic risk was associated with lower MetS prevalence (OR = 0.94, p = 1.84 × 10^–42) and its components (p < 2.30 × 10^–8). Meta-analyses of the replication cohorts showed nominal associations with MetS (p = 0.028) and 3 MetS components (p < 0.05). This work suggests individuals with a high polygenic risk for EL have a healthy metabolic profile promoting longevity.

人类健康的新陈代谢措施与长寿有关。失调导致代谢综合征 (MetS) 和负面健康结果。最近的异常长寿 (EL) 全基因组关联研究促进了对 EL 个体多基因风险评分 (PRS) 的估计。我们检验了 ELPRS 高的个体 MetS 患病率低的假设。参与者来自五组中年至老年人。主要分析在英国生物银行 (UKBB) 中进行（n  = 407,800，40–69 岁）。使用三项澳大利亚研究进行重复分析：亨特社区研究（n  = 2122，55-85 岁），澳大利亚老年双胞胎研究（n  = 539，65-90 岁）和悉尼记忆与衰老研究（n = 925，70-90 岁），以及瑞典哥德堡 H70 出生队列研究（n  = 2273，70-93 岁）。MetS 是使用既定标准定义的。对 ELPRS 和 MetS 及其组件进行了回归和荟萃分析。一般来说，MetS 患病率 (22–30%) 在老年群体中较高。在 UKBB 中，高 EL 多基因风险与较低的 MetS 患病率（OR = 0.94， p  = 1.84 × 10 ^–42）及其成分（p  < 2.30 × 10 ^{– 8}）相关。复制队列的荟萃分析显示与 MetS ( p  = 0.028) 和 3 MetS 组件 ( p < 0.05)。这项工作表明，具有高 EL 多基因风险的个体具有促进长寿的健康代谢特征。