Telomeres are specialised structures that cap the ends of chromosomes. They shorten with each cell division and have been proposed as a marker of cellular aging. Previous studies suggest that early life stressors increase the rate of telomere shortening with potential impact on disease states and mortality later in life. This study examined the associations between telomere length and exposure to a number of stressors that arise during development from the antenatal/perinatal period through to young adulthood. Participants were from the Christchurch Health and Development Study (CHDS), a New Zealand longitudinal birth cohort which has followed participants from birth until age 30. Telomere length was obtained on DNA from peripheral blood samples collected from consenting participants (n = 677) at age 28–30, using a quantitative PCR assay. These data were assessed for associations with 26 measures of life course adversity or stress which occurred prior to 25 years of age. No associations were found between telomere length measured at age 28–30 years and life course adversity or stress for specific measures and for the summary risk scores for each developmental domain. The correlations were very small ranging from ？0.06 to 0.06 with a median of 0.01, and none were statistically significant. Our results in this well-studied birth cohort do not support prior reports of such associations, and underscore the need for more extensive replication of proposed links between stress and telomere biology in larger cohorts with appropriate phenotypic data.
Blackburn EH, Gall JG (1978) A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. Journal of molecular biology 120: 33–53. doi: 10.1016/0022-2836(78)90294-2
[3]
Cawthon RM, Smith KR, O'Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361: 393–395. doi: 10.1016/s0140-6736(03)12384-7
[4]
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, et al. (2004) Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences of the United States of America 101: 17312–17315. doi: 10.1073/pnas.0407162101
[5]
Lin J, Epel E, Blackburn E (2012) Telomeres and lifestyle factors: roles in cellular aging. Mutation research 730: 85–89. doi: 10.1016/j.mrfmmm.2011.08.003
[6]
Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, et al.. (2013) Identification of seven loci affecting mean telomere length and their association with disease. Nature genetics 45: : 422–427, 427e421–422.
[7]
Mangino M, Hwang SJ, Spector TD, Hunt SC, Kimura M, et al. (2012) Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans. Human molecular genetics 21: 5385–5394. doi: 10.1093/hmg/dds382
[8]
Levy D, Neuhausen SL, Hunt SC, Kimura M, Hwang SJ, et al. (2010) Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. Proceedings of the National Academy of Sciences of the United States of America 107: 9293–9298. doi: 10.1073/pnas.0911494107
[9]
Codd V, Mangino M, van der Harst P, Braund PS, Kaiser M, et al. (2010) Common variants near TERC are associated with mean telomere length. Nature genetics 42: 197–199. doi: 10.1038/ng.532
[10]
Blackburn EH, Greider CW, Szostak JW (2006) Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nature medicine 12: 1133–1138. doi: 10.1038/nm1006-1133
[11]
Greider C, Blackburn E (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature.
[12]
Valdes aM, Andrew T, Gardner JP, Kimura M, Oelsner E, et al. (2005) Obesity, cigarette smoking, and telomere length in women. Lancet 366: 662–664. doi: 10.1016/s0140-6736(05)66630-5
[13]
Buxton JL, Walters RG, Visvikis-Siest S, Meyre D, Froguel P, et al. (2011) Childhood obesity is associated with shorter leukocyte telomere length. The Journal of clinical endocrinology and metabolism 96: 1500–1505. doi: 10.1210/jc.2010-2924
[14]
Nordfj？ll K, Eliasson M, Stegmayr B, Melander O, Nilsson P, et al. (2008) Telomere length is associated with obesity parameters but with a gender difference. Obesity (Silver Spring, Md) 16: 2682–2689. doi: 10.1038/oby.2008.413
[15]
Kim S, Parks CG, DeRoo LA, Chen H, Taylor JA, et al. (2009) Obesity and weight gain in adulthood and telomere length. Cancer Epidemiology Biomarkers & Prevention 18: 816–820. doi: 10.1158/1055-9965.epi-08-0935
[16]
Ehrlenbach S, Willeit P, Kiechl S, Willeit J, Reindl M, et al. (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: 1725–1734. doi: 10.1093/ije/dyp273
[17]
Harris SE, Deary IJ, MacIntyre A, Lamb KJ, Radhakrishnan K, et al. (2006) The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neuroscience letters 406: 260–264. doi: 10.1016/j.neulet.2006.07.055
[18]
Harris SE, Martin-Ruiz C, von Zglinicki T, Starr JM, Deary IJ (2012) Telomere length and aging biomarkers in 70-year-olds: the Lothian Birth Cohort 1936. Neurobiology of aging 33: 1486. e1483–1486. e1488. doi: 10.1016/j.neurobiolaging.2010.11.013
[19]
Damjanovic AK, Yang Y (2007) Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients. The Journal of Immunology 179: 4249–54. doi: 10.4049/jimmunol.179.6.4249
[20]
Parks CG, Miller DB, McCanlies EC, Cawthon RM, Andrew ME, et al. (2009) Telomere length, current perceived stress, and urinary stress hormones in women. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 18: 551–560. doi: 10.1158/1055-9965.epi-08-0614
[21]
Entringer S, Epel ES, Lin J, Buss C, Shahbaba B, et al. (2013) Maternal psychosocial stress during pregnancy is associated with newborn leukocyte telomere length. American journal of obstetrics and gynecology 208: 134.e131–137. doi: 10.1016/j.ajog.2012.11.033
[22]
Entringer S, Epel ES, Kumsta R, Lin J, Hellhammer DH, et al. (2011) Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences of the United States of America 108: E513–518. doi: 10.1073/pnas.1107759108
[23]
Tyrka AR, Price LH, Kao H-T, Porton B, Marsella Sa, et al. (2010) Childhood maltreatment and telomere shortening: preliminary support for an effect of early stress on cellular aging. Biological psychiatry 67: 531–534. doi: 10.1016/j.biopsych.2009.08.014
[24]
Kananen L, Surakka I, Pirkola S, Suvisaari J, L？nnqvist J, et al. (2010) Childhood adversities are associated with shorter telomere length at adult age both in individuals with an anxiety disorder and controls. PLoS One 5: e10826. doi: 10.1371/journal.pone.0010826
[25]
Kiecolt-Glaser JK, Gouin J-P, Weng N-P, Malarkey WB, Beversdorf DQ, et al. (2011) Childhood adversity heightens the impact of later-life caregiving stress on telomere length and inflammation. Psychosomatic medicine 73: 16–22. doi: 10.1097/psy.0b013e31820573b6
[26]
O'Donovan A, Epel E, Lin J, Wolkowitz O, Cohen B, et al. (2011) Childhood trauma associated with short leukocyte telomere length in posttraumatic stress disorder. Biological psychiatry 70: 465–471. doi: 10.1016/j.biopsych.2011.01.035
[27]
Shalev I, Moffitt TE, Sugden K, Williams B, Houts RM, et al.. (2012) Exposure to violence during childhood is associated with telomere erosion from 5 to 10 years of age: a longitudinal study. Molecular psychiatry.
[28]
Drury SS, Theall K, Gleason MM, Smyke aT, De Vivo I, et al. (2012) Telomere length and early severe social deprivation: linking early adversity and cellular aging. Molecular psychiatry 17: 719–727. doi: 10.1038/mp.2011.53
[29]
Surtees PG, Wainwright NWJ, Pooley Ka, Luben RN, Khaw K-T, et al. (2011) Life stress, emotional health, and mean telomere length in the European Prospective Investigation into Cancer (EPIC)-Norfolk population study. The journals of gerontology Series A, Biological sciences and medical sciences 66: 1152–1162. doi: 10.1093/gerona/glr112
[30]
Glass D, Parts L, Knowles D, Aviv A, Spector TD (2010) No correlation between childhood maltreatment and telomere length. 68: : e21-22; author reply e23–24.
[31]
Kao H-T, Cawthon RM, Delisi LE, Bertisch HC, Ji F, et al. (2008) Rapid telomere erosion in schizophrenia. Molecular psychiatry 13: 118–119. doi: 10.1038/sj.mp.4002105
[32]
Simon NM, Smoller JW, McNamara KL, Maser RS, Zalta AK, et al. (2006) Telomere shortening and mood disorders: preliminary support for a chronic stress model of accelerated aging. Biological psychiatry 60: 432–435. doi: 10.1016/j.biopsych.2006.02.004
[33]
Wolkowitz OM, Mellon SH, Epel ES, Lin J, Dhabhar FS, et al. (2011) Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress—preliminary findings. PloS one 6: e17837. doi: 10.1371/journal.pone.0017837
[34]
Shaffer Ja, Epel E, Kang MS, Ye S, Schwartz JE, et al. (2012) Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95), a population-based study. PLoS One 7: e48318. doi: 10.1371/journal.pone.0048318
[35]
Fergusson DM, Horwood LJ (2001) The Christchurch Health and Development Study: Review of findings on child and adolescent mental health. Australian and New Zealand Journal of Psychiatry 35: 287–296. doi: 10.1046/j.1440-1614.2001.00902.x
[36]
Fergusson DM, Horwood LJ, Ridder E (2005) Show me the child at seven: The consequences of conduct problems in childhood for psychosocial functioning in adulthood. Journal of Child Psychology and Psychiatry 46: 837–849. doi: 10.1111/j.1469-7610.2004.00387.x
[37]
Lahiri DK, Nurnberger JI (1991) A repid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic acides research. pp. 5444.
[38]
Cawthon RM (2002) Telomere measurement by quantitative PCR. Nucleic acids research 30: e47–e47. doi: 10.1093/nar/30.10.e47
[39]
Cawthon RM (2009) Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic acids research 37: e21–e21. doi: 10.1093/nar/gkn1027
[40]
Allshire RC, Dempster M, Hastie ND (1989) Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic acids research 17: 4611–4627. doi: 10.1093/nar/17.12.4611
[41]
Aviv A, Hunt SC, Lin J, Cao X, Kimura M, et al. (2011) Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucleic acids research 39: e134–e134. doi: 10.1093/nar/gkr634
[42]
Fergusson DM, Boden JM, Horwood LJ (2008) Exposure to childhood sexual and physical abuse and adjustment in early adulthood. Child Abuse and Neglect 32: 607–619. doi: 10.1016/j.chiabu.2006.12.018
[43]
Fergusson DM, Horwood LJ, Woodward LJ (2000) The stability of child abuse reports: A longitudinal study of young adults. Psychological Medicine 30: 529–544. doi: 10.1017/s0033291799002111
[44]
Parker G, Tupling H, Brown LB (1979) A Parental Bonding Instrument. British Journal of Medical Psycholog 52: 1–10. doi: 10.1111/j.2044-8341.1979.tb02487.x
[45]
Raudino A, Fergusson DM, Horwood LJ (2013) The quality of parent/child relationships in adolescence is associated with poor adult psychosocial adjustment. Journal of Adolescence 36: 331–340. doi: 10.1016/j.adolescence.2012.12.002
[46]
Straus MA (1979) Measuring intrafamily conflict and violence: The conflict tactics (CT) scale. Journal of Marriage and Family 41: 75–88. doi: 10.2307/351733
[47]
Fergusson DM, Horwood LJ (1998) Exposure to interparental violence in childhood and psychosocial adjustment in young adulthood. Child Abuse and Neglect 22: 339–357. doi: 10.1016/s0145-2134(98)00004-0
[48]
World Health Organization (1993) Composite International Diagnostic Interview (CIDI). Geneva, Switzerland: World Health Organization.
[49]
American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington DC: American Psychiatric Association.
[50]
Mulder RT, Fergusson DM, Horwood LJ (2013) Post-traumatic stress disorder symptoms form a traumatic and non-traumatic stress response dimension. Australian and New Zealand Journal of Psychiatry.
[51]
Fergusson DM, Horwood LJ, Miller A, Kennedy MA (2011) Life stress, 5HTTLPR and mental disorder: Findings from a 30 year longitudinal study. British Journal of Psychiatry 198: 129–135. doi: 10.1192/bjp.bp.110.085993
[52]
Cohen J (1988) Statistical Power Analysis for the Behavioural Sciences. Hillsdale, New Jersey: Lawrence Erlbaum Associates.
[53]
Epel E, Daubenmier J, Moskowitz JT, Folkman S, Blackburn E (2009) Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres. Annals of the New York Academy of Sciences 1172: 34–53. doi: 10.1111/j.1749-6632.2009.04414.x
[54]
Aviv A, Valdes AM, Spector TD (2006) Human telomere biology: pitfalls of moving from the laboratory to epidemiology. Int J Epidemiol 35: 1424–1429. doi: 10.1093/ije/dyl169
[55]
Vera E, Blasco MA (2012) Beyond average: potential for measurement of short telomeres. Aging (Albany NY) 4: 379–392.
[56]
Chen W, Kimura M, Kim S, Cao X, Srinivasan SR, et al. (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 66: 312–319. doi: 10.1093/gerona/glq223
[57]
Steenstrup T, Hjelmborg JV, Kark JD, Christensen K, Aviv A (2013) The telomere lengthening conundrum—artifact or biology? Nucleic acids research 41: e131. doi: 10.1093/nar/gkt370
