A1 Refereed original research article in a scientific journal
Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults
Authors: Mäkinen Ville-Petteri, Karsikas Mari, Kettunen Johannes, Lehtimäki Terho, Kähönen Mika, Viikari Jorma, Perola Markus, Salomaa Veikko, Järvelin Marjo-Riitta, Raitakari Olli T, Ala-Korpela Mika
Publisher: OXFORD UNIV PRESS
Publication year: 2022
Journal: International Journal of Epidemiology
Journal name in source: INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
Journal acronym: INT J EPIDEMIOL
Volume: 51
Issue: 6
First page : 1970
Last page: 1983
Number of pages: 14
ISSN: 0300-5771
DOI: https://doi.org/10.1093/ije/dyac062
Web address : https://doi.org/10.1093/ije/dyac062
Background: Quantification of metabolic changes over the human life course is essential to understanding ageing processes. Yet longitudinal metabolomics data are rare and long gaps between visits can introduce biases that mask true trends. We introduce new ways to process quantitative time-series population data and elucidate metabolic ageing trends in two large cohorts.
Methods: Eligible participants included 1672 individuals from the Cardiovascular Risk in Young Finns Study and 3117 from the Northern Finland Birth Cohort 1966. Up to three time points (ages 24-49 years) were analysed by nuclear magnetic resonance metabolomics and clinical biochemistry (236 measures). Temporal trends were quantified as median change per decade. Sample quality was verified by consistency of shared biomarkers between metabolomics and clinical assays. Batch effects between visits were mitigated by a new algorithm introduced in this report. The results below satisfy multiple testing threshold of P < 0.0006.
Results: Women gained more weight than men (+6.5% vs +5.0%) but showed milder metabolic changes overall. Temporal sex differences were observed for C-reactive protein (women +5.1%, men +21.1%), glycine (women +5.2%, men +1.9%) and phenylalanine (women +0.6%, men +3.5%). In 566 individuals with ≥+3% weight gain vs 561 with weight change ≤-3%, divergent patterns were observed for insulin (+24% vs -10%), very-low-density-lipoprotein triglycerides (+32% vs -6%), high-density-lipoprotein2 cholesterol (-6.5% vs +4.7%), isoleucine (+5.7% vs -6.0%) and C-reactive protein (+25% vs -22%).
Conclusion: We report absolute and proportional trends for 236 metabolic measures as new reference material for overall age-associated and specific weight-driven changes in real-world populations.