# A statistical approach to distinguish telomere elongation from error in longitudinal datasets

- 431 Downloads
- 4 Citations

## Abstract

Telomere length and the rate of telomere attrition vary between individuals and have been interpreted as the rate at which individuals have aged. The biology of telomeres dictates shortening with age, although telomere elongation with age has repeatedly been observed within a minority of individuals in several populations. These findings have been attributed to error, rather than actual telomere elongation, restricting our understanding of its possible biological significance. Here we present a method to distinguish between error and telomere elongation in longitudinal datasets, which is easy to apply and has few assumptions. Using simulations, we show that the method has considerable statistical power (>80 %) to detect even a small proportion (6.7 %) of TL increases in the population, within a relatively small sample (*N* = 200), while maintaining the standard level of Type I error rate (α ≤ 0.05).

### Keywords

Telomere length Statistics Telomere shortening Within individual Aging Human## Notes

### Acknowledgments

MJPS is supported by the Natural Environment Research Council (J024597/1) (United Kingdom). SN is supported by the Rutherford Discovery Fellowship (New Zealand). GS is supported by a grant by The Netherlands Organisation for Scientific Research (452-10-012), granted to M. Mills.

## Supplementary material

### References

- Aviv A, Chen W, Gardner JP, Kimura M, Brimacombe M, Cao X, Srinivasan SR, Berenson GS (2009) Leukocyte telomere dynamics: longitudinal findings among young adults in the Bogalusa Heart Study. Am J Epidemiol 169:323–329PubMedCrossRefGoogle Scholar
- Barrett ELB, Burke TA, Hammers M, Komdeur J, Richardson DS (2013) Telomere length and dynamics predict mortality in a wild longitudinal study. Mol Ecol 22:249–259PubMedCrossRefGoogle Scholar
- Beaulieu M, Reichert S, Le Maho Y, Ancel A, Criscuolo F (2011) Oxidative status and telomere length in a long-lived bird facing a costly reproductive event. Funct Ecol 25:577–585CrossRefGoogle Scholar
- Bize P, Criscuolo F, Metcalfe NB, Nasir L, Monaghan P (2009) Telomere dynamics rather than age predict life expectancy in the wild. Proc R Soc B 276:1679–1683 PubMedCrossRefGoogle Scholar
- Boonekamp JJ, Simons MJP, Hemerik L, Verhulst S (2013) Telomere length behaves as biomarker of somatic redundancy rather than biological age. Aging Cell 12:330–332PubMedCrossRefGoogle Scholar
- Chen W, Kimura M, Kim S, Cao X, Srinivasan SR, Berenson GS, Kark JD, Aviv A (2011) Longitudinal versus cross-sectional evaluations of leukocyte telomere length dynamics: age-dependent telomere shortening is the rule. J Gerontol A Biol Sci Med Sci 66A:312–319CrossRefGoogle Scholar
- Crawley MJ (2005) Statistics: an introduction using R. Wiley, ChichesterCrossRefGoogle Scholar
- Crawley MJ (2007) The R book. Wiley, ChichesterCrossRefGoogle Scholar
- Ehrlenbach S, Willeit P, Kiechl S, Willeit J, Reindl M, Schanda K, Kronenberg F, Brandstatter A (2009) Influences on the reduction of relative telomere length over 10 years in the population-based Bruneck Study: introduction of a well-controlled high-throughput assay. Int J Epidemiol 38:1725–1734PubMedCrossRefGoogle Scholar
- Epel ES, Merkin SS, Cawthon R, Blackburn EH, Adler NE, Pletcher MJ, Seeman TE (2009) The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men. Aging (Albany NY) 1:81–88Google Scholar
- Foote CG, Gault EA, Nasir L, Monaghan P (2011) Telomere dynamics in relation to early growth conditions in the wild in the lesser black-backed gull. J Zool 283:203–209CrossRefGoogle Scholar
- Gorbunova V, Seluanov A (2009) Coevolution of telomerase activity and body mass in mammals: from mice to beavers. Mech Ageing Dev 130:3–9Google Scholar
- Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci USA 109:1743–1748PubMedCrossRefGoogle Scholar
- Mather KA, Jorm AF, Parslow RA, Christensen H (2011) Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci 66:202–213PubMedCrossRefGoogle Scholar
- Nordfjäll K, Svenson U, Norrback K-F, Adolfsson R, Lenner P, Roos G (2009) The individual blood cell telomere attrition rate is telomere length dependent. PLoS Genet 5:e1000375PubMedCentralPubMedCrossRefGoogle Scholar
- R Development Core Team (2011) A language and environment for statistical computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
- Riethman H (2008) Human telomere structure and biology. Annu Rev Genomics Hum Genet 9:1–19PubMedCrossRefGoogle Scholar
- Salomons HM, Mulder GA, van de Zande L, Haussmann MF, Linskens MHK (2009) Telomere shortening and survival in free-living corvids. Proc R Soc B 276:3157–3165PubMedCrossRefGoogle Scholar
- Shalev I, Moffitt TE, Sugden K, Williams B, Houts RM, Danese A, Mill J, Arseneault L, Caspi A (2012) Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study. Mol Psychiatry 18:576–581PubMedCentralPubMedCrossRefGoogle Scholar
- Steenstrup T, Hjelmborg JB, Kark JD et al (2013) The telomere lengthening conundrum—artifact or biology? Nucleic Acids Res 14:e131CrossRefGoogle Scholar
- Wichura MJ (1988) Algorithm AS 241: the percentage points of the normal distribution. J R Stat Soc Ser C Appl Stat 37:477–484Google Scholar