Assessment of ageing using global mass-spectrometry based metabolomics: A cross-cohort longitudinal study in the UK and Ireland

Abstract Introduction Understanding the links between metabolism, ageing and age-related phenotypes may clarify the role of ageing in disease onset and improve risk prediction. Methods We conducted a cross-cohort assessment of biological age using broad-spectrum LC-MS metabolomics in 2,295 participants, aged 20-89, from the UK Airwave study (N=960) and The Irish Longitudinal Study of Ageing (N=1,335). Results N 2 ,N 2 -dimethylguanosine, C-glycosyltryptophan, bile acid glucuronides, and zeta-carotene were associated with chronological age, frailty, and mortality. We developed a metabolomic clock that was highly predictive of chronological age (r = 0.92) in test samples. Metabolomic age acceleration was strongly correlated between study visits ( r > 0.6). Each standard deviation higher metabolomic age acceleration (∼5 years) was associated with 43% higher mortality risk, 27% higher risk of mild cognitive impairment, and 10% increased risk of a higher frailty score in fully adjusted models. Discussion Our metabolomic clock provides a reproducible marker of generalised age-related disease risk.