Longitudinal profiling of metabolic ageing trends in two population cohorts of young adults

Ville-Petteri Mäkinen, Mari Karsikas, Johannes Kettunen, Terho Lehtimäki, Mika Kähönen, Jorma Viikari, Markus Perola, Veikko Salomaa, Marjo-Riitta Järvelin, Olli T Raitakari, Mika Ala-Korpela

Research output: Contribution to journalArticleScientificpeer-review


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.

Original languageEnglish
Pages (from-to)1970-1983
Number of pages14
JournalInternational Journal of Epidemiology
Issue number6
Publication statusPublished - 13 Dec 2022
Publication typeA1 Journal article-refereed


  • Humans
  • Female
  • Young Adult
  • Male
  • Adult
  • Middle Aged
  • C-Reactive Protein
  • Metabolomics/methods
  • Biomarkers
  • Magnetic Resonance Spectroscopy
  • Aging
  • Risk Factors

Publication forum classification

  • Publication forum level 3

ASJC Scopus subject areas

  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine


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