Telomere length regulators are activated in young men after pediatric kidney transplantation compared to healthy controls and survivors of childhood cancer-A cross-sectional study

Pediatr Transplant. 2019 Nov;23(7):e13550. doi: 10.1111/petr.13550. Epub 2019 Jul 11.

Abstract

Chronic diseases are known to cause premature aging and frailty. Data about telomere length and telomere length-regulating proteins after pediatric KTx are scarce. Leukocyte telomere length and gene expression level of eight telomere-binding proteins were analyzed in 20 KTx recipients, eight childhood NBL survivors, and nine healthy controls. The influence of key clinical parameters on telomere length and on regulators of telomere length was evaluated. The telomere length in the KTx recipients tended to be shorter (0.53 AU) than in the healthy controls (0.64 AU) but longer than in the NBL survivors (0.38 AU). There was no significant difference in telomere length between the NBL survivors and the KTx recipients (P = .110). The gene expression level of telomere length-preserving protein RPA1 was significantly higher in the KTx recipients than among the NBL survivors or healthy controls, while the expression of TRF2 and the tumor suppressor gene p16 was significantly higher in the KTX recipients when compared to the controls. TRF2 and TIN2 correlated significantly with hsCRP; additionally, TRF2 showed significant correlation with plasma creatinine and eGFR. KTx recipients have near to normal telomere length, but they have significantly higher gene expression levels of telomere regulatory proteins compared with healthy controls, suggesting activation of mechanisms preserving telomere length among KTx recipients. Our results suggest that declined graft function and consequent inflammatory response may have influence on telomerase activity.

Keywords: adolescent; adult; follow-up; kidney transplantation; telomerase; telomere.

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / metabolism
  • Cancer Survivors*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Humans
  • Kidney Transplantation*
  • Male
  • Telomere Shortening*
  • Telomere-Binding Proteins / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Telomere-Binding Proteins