title: Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule.
abstract: BACKGROUND
  Leukocyte telomere length (LTL) is considered a biomarker of human aging and based on cross-sectional studies it shortens with age. However, longitudinal studies reported that many adults display LTL lengthening.
  
  
  METHODS
  Using Southern blots, we compared cross-sectional rates of age-related LTL change across a ∼20 year age range with those based on longitudinal evaluations in three surveys (S1, S2, and S3) with three time intervals: S1-S2 (5.8 years), S2-S3 (6.6 years), and S1-S3 (12.4 years). Hierarchical linear modeling was used to explore LTL dynamics using LTL data from S1, S2, and S3.
  
  
  RESULTS
  Cross-sectionally, mean LTL shortenings were 24.6, 25.4, and 23.6 bp/y at S1, S2, and S3, respectively. Longitudinally, more variation was observed in the rate of LTL change during the shorter than longer follow-up periods. Furthermore, using simple differences in LTL, 14.4% and 10.7% of individuals displayed LTL lengthening during S1-S2 and S2-S3, respectively, but only 1.5% during S1-S3 (p < 0.001). The estimated mean rate of LTL shortening based on averaging empirical Bayes' estimates of LTL from a parsimonious hierarchical linear modeling model was 31 bp/y with a range from 23 to 47 bp/y with none of the participants showing LTL lengthening over the average 12.4 years of follow-up.
  
  
  CONCLUSIONS
  As aging displays a unidirectional progression, it is unlikely that LTL elongates with age. LTL elongation in longitudinal studies primarily reflects measurement errors of LTL in relation to the duration of follow-up periods.
authors.affiliation: Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Kim
authors.forename: X
authors.initials: X
authors.lastname: Cao
authors.forename: S R
authors.initials: SR
authors.lastname: Srinivasan
authors.forename: G S
authors.initials: GS
authors.lastname: Berenson
authors.forename: J D
authors.initials: JD
authors.lastname: Kark
authors.forename: A
authors.initials: A
authors.lastname: Aviv
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000502:physiology*