Metabolomic age (MileAge) predicts health and life span: A comparison of multiple machine learning algorithms

Biological aging clocks produce age estimates that can track with age-related health outcomes. This study aimed to benchmark machine learning algorithms, including regularized regression, kernel-based methods, and ensembles, for developing metabolomic aging clocks from nuclear magnetic resonance spectroscopy data. The UK Biobank data, including 168 plasma metabolites from up to <i>N</i> = 225,212 middle-aged and older adults (mean age, 56.97 years), were used to train and internally validate 17 algorithms. Metabolomic age (MileAge) delta, the difference between metabolite-predicted and chronological age, from a Cubist rule-based regression model showed the strongest associations with health and aging markers. Individuals with an older MileAge were frailer, had shorter telomeres, were more likely to suffer from chronic illness, rated their health worse, and had a higher all-cause mortality hazard (HR = 1.51; 95% CI, 1.43 to 1.59; <i>P</i> < 0.001). This metabolomic aging clock (MileAge) can be applied in research and may find use in health assessments, risk stratification, and proactive health tracking.