A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-09-15 DOI:10.1038/s41467-024-52310-9

Shiyu Zhang, Zheng Wang, Yijing Wang, Yixiao Zhu, Qiao Zhou, Xingxing Jian, Guihu Zhao, Jian Qiu, Kun Xia, Beisha Tang, Julian Mutz, Jinchen Li, Bin Li

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Abstract

The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate “biomarker - disease” causal pairs at the nominal significance level. We develop a metabolomic aging score that outperforms other aging metrics in predicting short-term mortality risk and exhibits strong potential for discriminating aging-accelerated populations and improving disease risk prediction. A longitudinal analysis of 13,263 individuals enables us to calculate a metabolomic aging rate which provides more refined aging assessments and to identify candidate anti-aging and pro-aging NMR biomarkers. Taken together, our study has presented a comprehensive aging-related metabolomic profile and highlighted its potential for personalized aging monitoring and early disease intervention.

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英国生物库 250,341 人生物衰老的代谢组学概况

衰老的代谢组学特征非常复杂。在这里，我们分析了来自 250,341 名英国生物库参与者的 325 个核磁共振 (NMR) 生物标志物，确定了 54 个与全因死亡率相关的代表性衰老相关生物标志物。我们利用 95,372 人的全基因组测序 (WGS) 数据对这 325 个生物标记物进行了全基因组关联研究 (GWAS)，并进行了多变量孟德尔随机化 (MVMR) 分析，在名义显著性水平上发现了 439 个候选 "生物标记物-疾病 "因果对。我们开发的代谢组衰老评分在预测短期死亡风险方面优于其他衰老指标，在区分衰老加速人群和改善疾病风险预测方面表现出强大的潜力。对 13,263 人的纵向分析使我们能够计算代谢组老化率，从而提供更精细的老化评估，并确定候选的抗衰老和促衰老 NMR 生物标记物。总之，我们的研究提出了一个全面的与衰老相关的代谢组图谱，并强调了其在个性化衰老监测和早期疾病干预方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.

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