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

doi:10.1038/s42003-022-03521-7

Genetic, parental and lifestyle factors influence telomere length

Commun Biol. 2022 Jun 9;5(1):565. doi: 10.1038/s42003-022-03521-7.

Authors

Sergio Andreu-Sánchez^#^{1

2}, Geraldine Aubert^#^{3

4}, Aida Ripoll-Cladellas^#⁵, Sandra Henkelman^#⁶, Daria V Zhernakova^{7

8}, Trishla Sinha⁷, Alexander Kurilshikov⁷, Maria Carmen Cenit^{7

9}, Marc Jan Bonder^{7

10

11}, Lude Franke⁷, Cisca Wijmenga⁷, Jingyuan Fu^{7

12}, Monique G P van der Wijst⁷, Marta Melé⁵, Peter Lansdorp^{13

14

15}, Alexandra Zhernakova¹⁶

Affiliations

¹ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [email protected].
² Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [email protected].
³ Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada.
⁴ Repeat Diagnostics Inc, Vancouver, BC, Canada.
⁵ Life Sciences Department, Barcelona Supercomputing Center, 08034, Barcelona, Catalonia, Spain.
⁶ European Research Institute for the Biology of Ageing, University of Groningen, Groningen, the Netherlands.
⁷ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁸ Laboratory of Genomic Diversity, Center for Computer Technologies, ITMO University, St. Petersburg, 197101, Russia.
⁹ Microbial Ecology, Nutrition, and Health Research Unit, Institute of Agrochemistry and Food Technology (IATA-CSIC), 46980, Paterna-Valencia, Spain.
¹⁰ Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany.
¹¹ European Molecular Biology Laboratory, Genome Biology Unit, 69117, Heidelberg, Germany.
¹² Department of Pediatrics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
¹³ Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, BC, Canada. [email protected].
¹⁴ European Research Institute for the Biology of Ageing, University of Groningen, Groningen, the Netherlands. [email protected].
¹⁵ Departments of Hematology and Medical Genetics, University of British Columbia, Vancouver, BC, Canada. [email protected].
¹⁶ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. [email protected].

^# Contributed equally.

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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging* / genetics
Epigenesis, Genetic
Female
Humans
Life Style
Parents
Pregnancy
Telomere* / genetics