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We conducted a cross-cohort assessment of biological age using broad-spectrum LC\u2013MS metabolomics of 3,686 plasma samples in 2,295 participants, aged 20\u201389, from the UK Airwave study (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u2009960) and the Irish Longitudinal Study of Ageing (\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20091,335). The nucleoside N\n                    <jats:sub>2<\/jats:sub>\n                    ,N\n                    <jats:sub>2<\/jats:sub>\n                    -dimethylguanosine, C-glycosyltryptophan, bile acid glucuronides, and the antioxidant zeta-carotene were associated with chronological age, frailty, and mortality. The noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol sulphate and the oligosaccharide sialyllactose were strongly associated with both age and mortality. We developed a metabolomic clock that was highly predictive of chronological age (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009=\u20090.92) in test samples. Metabolomic age acceleration was strongly correlated between study visits (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009&gt;\u20090.6). Each standard deviation increase in metabolomic age acceleration (~\u20095 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. The metabolites identified here may link ageing and age-related vulnerability and should be further investigated in mechanistic studies. The metabolomic clock has potential for translational applications, including as a prognostic and response marker of generalised age-related disease risk.\n                  <\/jats:p>","DOI":"10.1007\/s11357-026-02412-7","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:10:00Z","timestamp":1784646600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A metabolomic clock of population ageing: cross-cohort validation and associations with frailty and cognitive function\u00a0"],"prefix":"10.1007","author":[{"given":"Chung-Ho E.","family":"Lau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Chekmeneva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling M.","family":"O\u2019Halloran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K. 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