Tracking and fixed ranking of leukocyte telomere length across the adult life course

Abstract

Short leukocyte telomere length (LTL) is associated with atherosclerosis in adults and diminished survival in the elderly. LTL dynamics are defined by LTL at birth, which is highly variable, and its age-dependent attrition thereafter, which is rapid during the first 20 years of life. We examined whether age-dependent LTL attrition during adulthood can substantially affect individuals' LTL ranking (e.g., longer or shorter LTL) in relation to their peers. We measured LTL in samples donated 12 years apart on average by 1156 participants in four longitudinal studies. We observed correlations of 0.91-0.96 between baseline and follow-up LTLs. Ranking individuals by deciles revealed that 94.1% (95% confidence interval of 92.6-95.4%) showed no rank change or a 1 decile change over time. We conclude that in adults, LTL is virtually anchored to a given rank with the passage of time. Accordingly, the links of LTL with atherosclerosis and longevity appear to be established early in life. It is unlikely that lifestyle and its modification during adulthood exert a major impact on LTL ranking.

Keywords: Southern blots; human; leukocytes; longitudinal; telomeres.

Figure 1

Tracking of leukocyte telomere length (LTL) between baseline and follow-up examinations. Correlation between baseline LTL and follow-up LTL in the Jerusalem Lipid Research Clinic (LRC), the Bogalusa Heart Study (BHS), the Evolution de la Rigidite Arterielle (ERA), and the Longitudinal Study of Elderly Danish Twins (LSADT). The dotted lines are the identity lines, while the continuous lines are the linear regressions of the data. The R² (based on Pearson correlations) ranged from 0.82 for the LSADT to 0.93 for the ERA.

Figure 2

Ranking of leukocyte telomere length (LTL) by deciles for the baseline and follow-up examinations (left panel) and the percentage of subjects experiencing change (Δ) in decile rank at follow-up examination (right panel). Data are from all cohorts jointly. Left panel shows shift to a shorter LTL between baseline and follow-up examinations for each decile. Right panel shows the distribution of Δ between baseline and follow-up examinations. Negative sign denotes a downward shift in ranking, while positive sign indicates an upward shift in ranking. Additional data regarding individual cohorts are provided online in Supplementary Information, Fig. S1, and Table S2 (Supporting information).

Figure 3

The percentage of subjects in each decile experiencing change (Δ) in rank at follow-up examination. Data are from all cohorts jointly. The following are illustrations of the display: consider decile # 1 (the lowest decile), 14.7% of individuals ranked in this decile at follow-up were ranked in decile #2 at baseline (i.e., one decile downward shift). Now consider decile 2, 16.4% of individuals ranked in this decile at follow-up were ranked at baseline in decile #3 (i.e., one decile downward shift), 3.4% were ranked in decile # 4 (i.e., two deciles downward shift), and 13.8% in decile #1 (i.e., one decile upward shift). The same principle holds across all deciles.

Figure 4

Illustrative gel of Southern blots of the terminal restriction fragments (TRFs) from the Jerusalem Lipid Research Clinic study. A sample of known TRF length serves as an internal reference (R). Eight molecular weight (M) ladders are resolved at intervals across the gel, and the one that is closest to a given sample is used for the computation of the mean TRF for that sample. Baseline (B) and follow-up (F) of the mean TRFs (i.e., leukocyte telomere lengths) are shown (in kb) at the bottom of the lanes.