Journal
AGING-US
Volume 8, Issue 7, Pages 1398-1415Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100995
Keywords
telomere length; longitudinal decline; aging; genetic risk score; latent growth curve
Categories
Funding
- NIH [R01 AG04563, AG10175, AG028555]
- MacArthur Foundation Research Network on Successful Aging
- Swedish Council for Working Life and Social Research (FAS/FORTE) [97:0147:1B, 2009-0795, 2013-2292]
- Swedish Research Council [825-2007-7460, 825-2009-6141, 521-2013-8689, 2015-03255]
- Loo & Hans Osterman Foundation
- Foundation for Geriatric Diseases
- Marie Curie intra-European Fellowship of the European Community's Seventh Framework Programme [PIEF-GA-2011-300355]
- Distinguished Professor Award from the Karolinska Institutet
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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 similar to 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.
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