title: Longitudinal decline of leukocyte telomere length in old age and the association with sex and genetic risk.
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.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Berglund
authors.affiliation: Department of Psychology, University of California-Riverside, Riverside, CA 92521, USA.
authors.forename: Chandra A
authors.initials: CA
authors.lastname: Reynolds
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploner
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.|Department of Clinical Psychology, Faculty of Social Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: Lotte
authors.initials: L
authors.lastname: Gerritsen
authors.affiliation: Department of Biosciences, Viikki Biocenter, University of Helsinki, Helsinki, Finland.|Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Iiris
authors.initials: I
authors.lastname: Hovatta
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Hägg
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012737:Sex Factors; D016615:Telomere
keywords: aging; genetic risk score; latent growth curve; longitudinal decline; telomere length