Fat metabolism is associated with telomere length in six population-based studies

BBMRI Metabolomics Consortium, Ashley Van Der Spek, Hata Karamujić-Čomić, René Pool, Mariska Bot, Marian Beekman, Sanzhima Garmaeva, Pascal P. Arp, Sandra Henkelman, Jun Liu, Alexessander Couto Alves, Gonneke Willemsen, Gerard Van Grootheest, Geraldine Aubert, M. Arfan Ikram, Marjo Riitta Jarvelin, Peter Lansdorp, André G. Uitterlinden, Alexandra Zhernakova, P. Eline SlagboomBrenda W.J.H. Penninx, Dorret I. Boomsma, Najaf Amin, Cornelia M. Van Duijn*

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

11 Citaten (Scopus)
191 Downloads (Pure)

Samenvatting

Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold Pmeta = 6.5 × 10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-CE %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-CE) became significantly associated with LTL (P = 3.6 × 10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (P = 1.9 × 10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.

Originele taal-2English
Pagina's (van-tot)1159-1170
Aantal pagina's12
TijdschriftHuman Molecular Genetics
Volume31
Nummer van het tijdschrift7
DOI's
StatusPublished - 1-apr.-2022

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