Metabolic biomarkers using nuclear magnetic resonance metabolomics assay for the prediction of aging-related disease risk and mortality: a prospective, longitudinal, observational, cohort study based on the {UK} {Biobank}

Abstract

<p>The identification of metabolic biomarkers for aging-related diseases and mortality is of significant interest in the field of longevity. In this study, we investigated the associations between nuclear magnetic resonance (NMR) metabolomics biomarkers and aging-related diseases as well as mortality using the UK Biobank dataset. We analyzed NMR samples from approximately 110,000 participants and used multi-head machine learning classification models to predict the incidence of aging-related diseases. Cox regression models were then applied to assess the relevance of NMR biomarkers to the risk of death due to aging-related diseases. Additionally, we conducted survival analyses to evaluate the potential improvements of NMR in predicting survival and identify the biomarkers most strongly associated with negative health outcomes by dividing participants into health, disease, and death groups for all age groups. Our analysis revealed specific metabolomics profiles that were associated with the incidence of age-related diseases, and the most significant biomarker was intermediate density lipoprotein cholesteryl (IDL-CE). In addition, NMR biomarkers could provide additional contributions to relevant mortality risk prediction when combined with conventional risk factors, by improving the C-index from 0.813 to 0.833, with 17 NMR biomarkers significantly contributing to disease-related death, such as monounsaturated fatty acids (MUFA), linoleic acid (LA), glycoprotein acetyls (GlycA), and omega-3. Moreover, the value of free cholesterol in very large HDL particles (XL-HDL-FC) in the healthy control group demonstrated significantly higher values than the disease and death group across all age groups. This study highlights the potential of NMR metabolomics profiling as a valuable tool for identifying metabolic biomarkers associated with aging-related diseases and mortality risk, which could have practical implications for aging-related disease risk and mortality prediction.<br></p>