Genetic, parental and lifestyle factors influence telomere length

Andreu-Sanchez, S.; Aubert, G.; Ripoll-Cladellas, A.; Henkelman, S.; Zhernakova, D. V.; Sinha, T.; Kurilshikov, A.; Cenit, M. C.; Bonder, M. J.; Lifelines cohort study,; Franke, L.; Wijmenga, C.; Fu, J.; van der Wijst, M. G. P.; Mele, M.; Lansdorp, P.; Zhernakova, A.

doi:10.1101/2021.12.14.472541

bioRxiv · 10.1101/2021.12.14.472541

Genetic, parental and lifestyle factors influence telomere length

Andreu-Sanchez, S.·Aubert, G.·Ripoll-Cladellas, A.·Henkelman, S.·Zhernakova, D. V.·Sinha, T.·Kurilshikov, A.·Cenit, M. C.·Bonder, M. J.·Lifelines cohort study,·Franke, L.·Wijmenga, C.·Fu, J.·van der Wijst, M. G. P.·Mele, M.·Lansdorp, P.·Zhernakova, A.

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Abstract

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1,046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Coupling these measurements to single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.

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Andreu-Sanchez, S., Aubert, G., Ripoll-Cladellas, A., Henkelman, S., Zhernakova, D. V., Sinha, T., Kurilshikov, A., Cenit, M. C., Bonder, M. J., Lifelines cohort study,, Franke, L., Wijmenga, C., Fu, J., van der Wijst, M. G. P., Mele, M., Lansdorp, P., Zhernakova, A.. 2021-12-15. Genetic, parental and lifestyle factors influence telomere length. https://doi.org/10.1101/2021.12.14.472541

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