Determinants of accelerated metabolomic and epigenetic aging in a UK cohort. Issue 6 (3rd May 2020)

• Record Type: Journal Article
• Authors: Robinson, Oliver; Chadeau Hyam, Marc; Karaman, Ibrahim; Climaco Pinto, Rui; Ala-Korpela, Mika; Handakas, Evangelos; Fiorito, Giovanni; Gao, He; Heard, Andy; Jarvelin, Marjo‐Riitta; Lewis, Matthew; Pazoki, Raha; Polidoro, Silvia; Tzoulaki, Ioanna; Wielscher, Matthias; Elliott, Paul; Vineis, Paolo
• Is Part Of: Aging cell. Volume 19:Issue 6(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-05-03
• Subjects: accelerated aging -- affective mood disorders -- DNA methylation -- metabolomics -- molecular biology of aging -- risk factors; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13149
• Languages: English
• ISSNs: 1474-9718

Abstract

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. Abstract : We have developed a novel assessment of biological age using broad metabolomic profiling of small molecules circulating in blood and urine, collected from over 2, 000 working age adults. We compare this metabolomic age assessment with an established epigenetic 'clocks' and show that 'age acceleration' is associated with risk factors of premature mortality, including depression.