Abstract
Recent longitudinal studies of age-dependent leukocyte telomere length (LTL) attrition have reported that variable proportions of individuals experience LTL lengthening. Often, LTL lengthening has been taken at face value, and authors have speculated about the biological causation of this finding. Based on empirical data and theoretical considerations, we show that regardless of the method used to measure telomere length (Southern blot or quantitative polymerase chain reaction-based methods), measurement error of telomere length and duration of follow-up explain almost entirely the absence of age-dependent LTL attrition in longitudinal studies. We find that LTL lengthening is far less frequent in studies with long follow-up periods and those that used a high-precision Southern blot method (as compared with quantitative polymerase chain reaction determination, which is associated with larger laboratory error). We conclude that the LTL lengthening observed in longitudinal studies is predominantly, if not entirely, an artifact of measurement error, which is exacerbated by short follow-up periods. We offer specific suggestions for design of longitudinal studies of LTL attrition to diminish this artifact.
Highlights
Telomere length (TL) on average declines with age
Based on empirical data derived from the longitudinal studies presented in Table 1, the proportion of leukocyte telomere length (LTL) gainers was inversely related to the duration of the follow-up, i.e. the shorter the duration, the greater the e131 Nucleic Acids Research, 2013, Vol 41, No 13
With a CV of 3%, 8% of individuals would be misclassified as LTL gainers when (i) duplicate measurements are performed at baseline and follow-up examinations, (ii) the rate of LTL attrition is 30 bp/year and (iii) the follow-up duration is 10 years
Summary
Longitudinal studies in humans report varying proportions of subjects who ostensibly display TL lengthening over time (1–12). In this communication, we address the following question: does the lengthening of TL represent a true biological phenomenon or an artifact inherent in the measurement error of TL in relation to the duration of the follow-up period? We address the following question: does the lengthening of TL represent a true biological phenomenon or an artifact inherent in the measurement error of TL in relation to the duration of the follow-up period? Biological ‘noise’, arising from neither genes nor the environment, is a major explanation for the inter-individual variation in phenotypic expressions (13) This form of noise is largely beyond our control. If LTL elongation is an artifact, researchers need to optimize longitudinal studies of LTL dynamics (by using both measurement methods that minimize error and performing studies with extended follow-up) so that the overall effect of this artifact will be minimized or eliminated
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