TY - JOUR

T1 - Leukocyte telomere dynamics in the elderly

AU - Steenstrup, Troels

AU - Hjelmborg, Jacob V B

AU - Mortensen, Laust Hvas

AU - Kimura, Masayuki

AU - Christensen, Kaare

AU - Aviv, Abraham

PY - 2013/2

Y1 - 2013/2

N2 - Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants of the Longitudinal Study of Aging Danish Twins. We measured LTL by Southern blots of the terminal restriction fragment length (TRFL) in 476 individuals (73-94 years) in a cross-sectional evaluation and in a subset of this cohort comprising 80 individuals (73-81 years at baseline) who were followed-up for approximately 10 years. Based on the mean TRFL, we found that a) the average rate of LTL attrition was respectively, 27 bp/year (P < 0.001) and 31 bp/year (P < 0.001) for the cross-sectional and longitudinal evaluations, and b) mean TRFL was 180 bp (95 % CI 43, 320) longer in females than males (P < 0.010). For the TRFL distribution, which captures telomeres of all lengths in the DNA sample, we observed significant shifts with age toward shorter telomeres. Based on the measurement error of the TRFLs, we computed that in the longitudinal evaluation 10.6 % of individuals would manifest LTL elongation over 10 years, assuming a 340 bp attrition during this period. This was not significantly different from the empirical observation of 7.5 % of individuals showing LTL elongation. We conclude that accumulation of ultra-short telomeres in leukocytes of the elderly reflects a shift toward shorter telomeres in the entire telomere distribution. Measurement error is the probable explanation for LTL elongation in longitudinal studies.

AB - Limited data suggest that leukocytes of the elderly display ultra-short telomeres. It was reported that in some elderly persons leukocyte telomere length (LTL) shows age-dependent elongation. Using cross-sectional and longitudinal models, we characterized LTL dynamics in participants of the Longitudinal Study of Aging Danish Twins. We measured LTL by Southern blots of the terminal restriction fragment length (TRFL) in 476 individuals (73-94 years) in a cross-sectional evaluation and in a subset of this cohort comprising 80 individuals (73-81 years at baseline) who were followed-up for approximately 10 years. Based on the mean TRFL, we found that a) the average rate of LTL attrition was respectively, 27 bp/year (P < 0.001) and 31 bp/year (P < 0.001) for the cross-sectional and longitudinal evaluations, and b) mean TRFL was 180 bp (95 % CI 43, 320) longer in females than males (P < 0.010). For the TRFL distribution, which captures telomeres of all lengths in the DNA sample, we observed significant shifts with age toward shorter telomeres. Based on the measurement error of the TRFLs, we computed that in the longitudinal evaluation 10.6 % of individuals would manifest LTL elongation over 10 years, assuming a 340 bp attrition during this period. This was not significantly different from the empirical observation of 7.5 % of individuals showing LTL elongation. We conclude that accumulation of ultra-short telomeres in leukocytes of the elderly reflects a shift toward shorter telomeres in the entire telomere distribution. Measurement error is the probable explanation for LTL elongation in longitudinal studies.

KW - Age Factors

KW - Aged

KW - Aged, 80 and over

KW - Aging

KW - Blotting, Southern

KW - Cross-Sectional Studies

KW - Female

KW - Humans

KW - Leukocytes

KW - Longitudinal Studies

KW - Male

KW - Polymorphism, Restriction Fragment Length

KW - Telomere

U2 - 10.1007/s10654-013-9780-4

DO - 10.1007/s10654-013-9780-4

M3 - Journal article

C2 - 23430034

VL - 28

SP - 181

EP - 187

JO - European Journal of Epidemiology

JF - European Journal of Epidemiology

SN - 0393-2990

IS - 2

ER -