Determinants of accelerated metabolomic and epigenetic aging in a UK cohort

Oliver Robinson, Marc Chadeau Hyam, Ibrahim Karaman, Rui Climaco Pinto, Mika Ala-Korpela, Evangelos Handakas, Giovanni Fiorito, He Gao, Andy Heard, Marjo-Riitta Jarvelin, Matthew Lewis, Raha Pazoki, Silvia Polidoro, Ioanna Tzoulaki, Matthias Wielscher, Paul Elliott, Paolo Vineis

Research output: Contribution to journalArticlepeer-review

Abstract

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. We investigated the determinants of accelerated aging, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r = .86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.

Original languageEnglish
Pages (from-to)e13149
JournalAging Cell
Volume19
Issue number6
DOIs
Publication statusPublished - Jun 2020
Externally publishedYes

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