Genetic, parental and lifestyle factors influence telomere length

Sergio Andreu-Sánchez*, Geraldine Aubert, Aida Ripoll-Cladellas, Sandra Henkelman, Daria V Zhernakova, Trishla Sinha, Alexander Kurilshikov, Maria Carmen Cenit, Marc Jan Bonder, Lude Franke, Cisca Wijmenga, Jingyuan Fu, Monique G P van der Wijst, Marta Melé, Peter Lansdorp, Alexandra Zhernakova

*Corresponding author for this work

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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 1046 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. 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.

Original languageEnglish
Article number565
Number of pages13
JournalCommunications biology
Issue number1
Publication statusPublished - 9-Jun-2022

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