Correlates of longitudinal leukocyte telomere length in the Costa Rican Longevity Study of Healthy Aging (CRELES): On the importance of DNA collection and storage procedures.

David H. Rehkopf,Luis Rosero-Bixby,Jue Lin,Jorge Azofeifa,Elissa S. Epel,Alejandro Leal,William H. Dow

doi:10.1371/journal.pone.0223766

Abstract

The objective is to identify cofactors of leukocyte telomere length (LTL) in a Latin American population, specifically the association of LTL with 36 socio-demographic, early childhood, and health characteristics, as well as with DNA sample collection and storage procedures. The analysis is based on longitudinal information from a subsample of 1,261 individuals aged 60+ years at baseline from the Costa Rican Study of Longevity and Healthy Aging (CRELES): a nationally representative sample of elderly population. Random effects regression models for panel data were used to estimate the associations with LTL and its longitudinal changes. Sample collection procedures and DNA refrigerator storage time were strongly associated with LTL: telomeres are longer in blood collected in October-December, in DNA extracted from <1-year-old blood cells, and in DNA stored at 4°C for longer periods of time up to five years. The data confirmed that telomeres are shorter at older ages, as well as among males, and diabetic individuals, whereas telomeres are longer in the high-longevity Nicoya region. Most health, biomarkers, and early childhood indicators did not show significant associations with LTL. Longitudinal LTL variation over approximately two years was mainly associated with baseline LTL levels, as found in other studies. Our findings suggest that if there is unavoidable variability in season of sample collection and DNA storage time, these factors should be controlled for in all demographic and epidemiologic studies of LTL. However, due to unobserved components of measurement variation, statistical control may be inadequate as compared to standardization of data collection procedures.

Highlights

Telomeres are canonical repetitions of non-coding nucleotides and associated protective proteins at the end of chromosomes
In prior work in the CRELES data we reported that month of blood draw was associated with leukocyte telomere length (LTL) [31], and we attempt to replicate this finding in our new larger sample
Variables Telomere length T/S ratio Measurement factors Assay lot 2010 Oct-Dec blood draw DNA storage time

Summary

Introduction

Telomeres are canonical repetitions of non-coding nucleotides and associated protective proteins at the end of chromosomes. By protecting against the degradation of the coding regions of DNA, telomeres: 1) prevent the deletion of coding DNA sequence that would impact transcription and other processes, 2) prevent end to end chromosome fusions that would otherwise occur, and 3) prevent the cell from leaving the cell cycle and becoming senescent. In terms of environmental and behavioral correlates of leukocyte telomere length (LTL), the most consistent associations are with depression and severe stress [1, 2] and in some cases with measures of socioeconomic status that are established earlier in life [3, 4]. Newer literature has suggested that leukocyte telomere length may be most useful both on its own [9] and as part of composite measures of earlier life biological markers of the underlying aging process [10, 11]

Methods

Results

Conclusion