Longitudinal telomere length and body composition in healthy term-born infants during the first two years of life.

Anita C S Hokken-Koelega,Laura M Breij,Gabriele Saretzki,Matthew Denniff,Gerthe F Kerkhof,Nilesh J Samani,Inge A L P Van Beijsterveldt,Kirsten S De Fluiter,Veryan Codd,Marieke Abrahamse-Berkeveld

doi:10.1371/journal.pone.0246400

Abstract

ObjectiveLeukocyte telomere length (LTL) is one of the markers of biological aging as shortening occurs over time. Shorter LTL has been associated with adiposity and a higher risk of cardiovascular diseases. The objective was to assess LTL and LTL shortening during the first 2 years of life in healthy, term-born infants and to associate LTL shortening with potential stressors and body composition.Study designIn 145 healthy, term-born infants (85 boys), we measured LTL in blood, expressed as telomere to single-gene copy ratio (T/S ratio), at 3 months and 2 years by quantitative PCR technique. Fat mass (FM) was assessed longitudinally by PEAPOD, DXA, and abdominal FM by ultrasound.ResultsLTL decreased by 8.5% from 3 months to 2 years (T/S ratio 4.10 vs 3.75, p<0.001). LTL shortening from 3 months to 2 years associated with FM%(R = 0.254), FM index(R = 0.243) and visceral FM(R = 0.287) at 2 years. LTL shortening tended to associate with gain in FM% from 3 to 6 months (R = 0.155, p = 0.11), in the critical window for adiposity programming. There was a trend to a shorter LTL in boys at 2 years(p = 0.056). LTL shortening from 3 months to 2 years was not different between sexes.ConclusionWe present longitudinal LTL values and show that LTL shortens considerably (8.5%) during the first 2 years of life. LTL shortening during first 2 years of life was associated with FM%, FMI and visceral FM at age 2 years, suggesting that adverse adiposity programming in early life could contribute to more LTL shortening.

Highlights

Telomeres are noncoding repetitive DNA sequences at the end of chromosomes, protecting genomic DNA in maintaining stability [1]
Leukocyte telomere length (LTL) shortening tended to associate with gain in Fat mass (FM)% from 3 to 6 months (R = 0.155, p = 0.11), in the critical window for adiposity programming
As we previously found in the same study group that the gain in FM% from 3 to 6 months was associated with a higher FM% at 2 years, we investigated if the shortening in LTL from 3 months to 2 years was associated with the gain in FM% from 3 to 6 months

Summary

Introduction

Telomeres are noncoding repetitive DNA sequences at the end of chromosomes, protecting genomic DNA in maintaining stability [1]. Due to the inability of DNA polymerase to fully replicate the ends of chromosomes, telomeres shorten with each cell division, with increasing age. When telomeres are reduced to a critical length, cells enter a state of arrest (cell senescence) [2]. Telomere length can be used as a proxy of biological aging and mortality [3], it is not the only biomarker of aging. Shorter telomeres are associated with an increased risk for cardiovascular diseases (CVD), but it is uncertain if telomere length can be seen as prognostic marker for CVD [3]

Methods

Discussion

Conclusion