Abstract
Telomeres are DNA-protein structures at the ends of chromosomes. Leukocyte telomere length (LTL) shortening has been associated with advanced age. However, most studies use cross-sectional data, hence, the aim of our study was to model longitudinal trajectories of LTL attrition across 20 years at old age. Assessments of LTL were done by qPCR in SATSA (Swedish Adoption/Twin Study of Aging; N=636 individuals). Cross-sectional and longitudinal associations with age were estimated, the latter using latent growth curve analysis. A genetic risk score (GRS) for LTL was further assessed and included in the models. We confirmed an inverse cross-sectional association of LTL with age (B=−0.0022 T/S-ratio; 95% CI: −0.0035, −0.0009, p-value=0.0008). Longitudinal LTL analyses adjusted for sex (1598 samples; ≤5 measurements) suggested modest average decline until 69 years of age but accelerating decline after 69 years, with significant inter-individual variation. Women had on average ∼6% T/S-ratio units longer LTL at baseline, and inclusion of the GRS improved the model where four risk alleles was equivalent to the effect size difference between the sexes. In this cohort of old individuals, baseline LTL varied with age, sex and genetic background. The rate of change of LTL accelerated with age and varied considerably between individuals.
Highlights
Telomeres are DNA-protein structures of tandem hexanucleotide repeats at the ends of eukaryotic chromosomes, providing protection from degradation and recombination during cell division [1]
The Swedish Adoption/Twin Study of Aging (SATSA) [22] is a longitudinal study started in 1984 including twins from mid-life and onwards
Through linear regression adjusted for family relatedness and sex, an inverse association between Leukocyte telomere length (LTL) and age was found (B=-0.0022 T/Sratio/year; 95% confidence interval [CI]: -0.0035, 0.0009, p-value=0.0008) and female sex was associated with a greater overall LTL (0.0499; 95% CI: 0.0200, 0.0797; p-value=0.001)
Summary
Telomeres are DNA-protein structures of tandem hexanucleotide repeats at the ends of eukaryotic chromosomes, providing protection from degradation and recombination during cell division [1]. Leukocyte telomere length (LTL) in humans is inversely associated with age and is influenced by genetic [3] and environmental factors [4]. A recent meta-analysis of 124 cross-sectional studies has shown that telomere lengths are significantly shorter with age [15], and at least six longitudinal studies report a decrease in telomere length with advancing age [1621]. Previous efforts have had shorter followup time and only included two to three time points per study subject, which is insufficient for estimating trajectories of change. We examine both the cross-sectional and longitudinal associations between LTL and chronological age in elderly Swedish twins with up to five LTL measurements per individual across 20 years. We sought to characterize LTL trajectories with advancing age, and to test whether www.impactaging.com
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