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Stressful life events and leukocyte telomere attrition in adulthood: a prospective population-based cohort study

Published online by Cambridge University Press:  29 July 2015

S. L. van Ockenburg
Affiliation:
Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, The Netherlands
E. H. Bos
Affiliation:
Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, The Netherlands
P. de Jonge
Affiliation:
Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, The Netherlands
P. van der Harst
Affiliation:
Department of Cardiology, University of Groningen, University Medical Center Groningen, The Netherlands
R. O. B. Gans
Affiliation:
Department of Internal Medicine, University of Groningen, University Medical Center Groningen, The Netherlands
J. G. M. Rosmalen*
Affiliation:
Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, The Netherlands
*
* Address for correspondence: Professor J. G. M. Rosmalen, Interdisciplinary Center Psychopathology and Emotion regulation, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, CC72, Groningen, The Netherlands (Email: [email protected])

Abstract

Background.

Telomere attrition might be one of the mechanisms through which psychosocial stress leads to somatic disease. To date it is unknown if exposure to adverse life events in adulthood is associated with telomere shortening prospectively. In the current study we investigated whether life events are associated with shortening of telomere length (TL).

Method.

Participants were 1094 adults (mean age 53.1, range 33–79 years) from the PREVEND cohort. Data were collected at baseline (T1) and at two follow-up visits after 4 years (T2) and 6 years (T3). Life events were assessed with an adjusted version of the List of Threatening Events (LTE). TL was measured by monochrome multiplex quantitative PCR at T1, T2, and T3. A linear mixed model was used to assess the effect of recent life events on TL prospectively. Multivariable regression analyses were performed to assess whether the lifetime life events score or the score of life events experienced before the age of 12 predicted TL cross-sectionally. All final models were adjusted for age, sex, body mass index, presence of chronic diseases, frequency of sports, smoking status, and level of education.

Results.

Recent life events significantly predicted telomere attrition prospectively (B = −0.031, p = 0.007). We were not able to demonstrate a significant cross-sectional relationship between the lifetime LTE score and TL. Nor did we find exposure to adverse life events before the age of 12 to be associated with TL in adulthood.

Conclusions.

Exposure to recent adverse life events in adulthood is associated with telomere attrition prospectively.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

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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. American Journal of Epidemiology 169, 323329.CrossRefGoogle ScholarPubMed
Aviv, A, Hunt, SC, Lin, J, Cao, X, Kimura, M, Blackburn, E (2011). Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR. Nucleic Acids Research 39, e134.CrossRefGoogle ScholarPubMed
Aviv, A, Valdes, AM, Spector, TD (2006). Human telomere biology: pitfalls of moving from the laboratory to epidemiology. International Journal of Epidemiology 35, 14241429.CrossRefGoogle ScholarPubMed
Barrett, EL, Richardson, DS (2011). Sex differences in telomeres and lifespan. Aging Cell 10, 913921.CrossRefGoogle ScholarPubMed
Beery, AK, Lin, J, Biddle, JS, Francis, DD, Blackburn, EH, Epel, ES (2012). Chronic stress elevates telomerase activity in rats. Biology Letters 8, 10631066.CrossRefGoogle ScholarPubMed
Ben-Shlomo, Y, Kuh, D (2002). A life course approach to chronic disease epidemiology: conceptual models, empirical challenges and interdisciplinary perspectives. International Journal of Epidemiology 31, 285293.CrossRefGoogle ScholarPubMed
Brugha, TS, Cragg, D (1990). The List of Threatening Experiences: the reliability and validity of a brief life events questionnaire. Acta Psychiatrica Scandinavica 82, 7781.CrossRefGoogle ScholarPubMed
Cawthon, RM (2009). Telomere length measurement by a novel monochrome multiplex quantitative PCR method. Nucleic Acids Research 37, e21.CrossRefGoogle ScholarPubMed
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, 393395.CrossRefGoogle ScholarPubMed
Chan, SW, Blackburn, EH (2002). New ways not to make ends meet: telomerase, DNA damage proteins and heterochromatin. Oncogene 21, 553563.CrossRefGoogle 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. Journal of Gerontology, Series A, Biological Sciences and Medical Sciences 66, 312319.CrossRefGoogle ScholarPubMed
Chida, Y, Hamer, M (2008). Chronic psychosocial factors and acute physiological responses to laboratory-induced stress in healthy populations: a quantitative review of 30 years of investigations. Psychological Bulletin 134, 829885.CrossRefGoogle ScholarPubMed
Chida, Y, Steptoe, A (2010). Greater cardiovascular responses to laboratory mental stress are associated with poor subsequent cardiovascular risk status: a meta-analysis of prospective evidence. Hypertension 55, 10261032.CrossRefGoogle ScholarPubMed
Du, M, Prescott, J, Kraft, P, Han, J, Giovannucci, E, Hankinson, SE, De Vivo, I (2012). Physical activity, sedentary behavior, and leukocyte telomere length in women. American Journal of Epidemiology 175, 414422.CrossRefGoogle ScholarPubMed
Epel, ES, Blackburn, EH, Lin, J, Dhabhar, FS, Adler, NE, Morrow, JD, Cawthon, RM (2004). Accelerated telomere shortening in response to life stress. Proceedings of the National Academy of Sciences USA 101, 1731217315.CrossRefGoogle ScholarPubMed
Epel, ES, Lin, J, Wilhelm, FH, Wolkowitz, OM, Cawthon, R, Adler, NE, Dolbier, C, Mendes, WB, Blackburn, EH (2006). Cell aging in relation to stress arousal and cardiovascular disease risk factors. Psychoneuroendocrinology 31, 277287.CrossRefGoogle ScholarPubMed
Flores, I, Cayuela, ML, Blasco, MA (2005). Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 12531256.CrossRefGoogle ScholarPubMed
Hardt, J, Rutter, M (2004). Validity of adult retrospective reports of adverse childhood experiences: review of the evidence. Journal of Child Psychology and Psychiatry, and Allied Disciplines 45, 260273.CrossRefGoogle ScholarPubMed
Harley, CB, Futcher, AB, Greider, CW (1990). Telomeres shorten during ageing of human fibroblasts. Nature 345, 458460.CrossRefGoogle ScholarPubMed
Hoen, PW, Rosmalen, JG, Schoevers, RA, Huzen, J, van der Harst, P, de Jonge, P (2013). Association between anxiety but not depressive disorders and leukocyte telomere length after 2 years of follow-up in a population-based sample. Psychological Medicine 43, 689697.CrossRefGoogle ScholarPubMed
Honig, LS, Schupf, N, Lee, JH, Tang, MX, Mayeux, R (2006). Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia. Annals of Neurology 60, 181187.CrossRefGoogle ScholarPubMed
Huzen, J, Peeters, W, de Boer, RA, Moll, FL, Wong, LS, Codd, V, de Kleijn, DP, de Smet, BJ, van Veldhuisen, DJ, Samani, NJ, van Gilst, WH, Pasterkamp, G, van der Harst, P (2011). Circulating leukocyte and carotid atherosclerotic plaque telomere length: interrelation, association with plaque characteristics, and restenosis after endarterectomy. Arteriosclerosis, Thrombosis, and Vascular Biology 31, 12191225.CrossRefGoogle ScholarPubMed
Kenward, MG, Molenberghs, G (1998). Likelihood based frequentist inference when data are missing at random. Statistical Science 13, 236247.CrossRefGoogle Scholar
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732741.CrossRefGoogle ScholarPubMed
Miller, GE, Chen, E, Zhou, ES (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin 133, 2545.CrossRefGoogle ScholarPubMed
Nordfjall, K, Svenson, U, Norrback, KF, Adolfsson, R, Lenner, P, Roos, G (2009). The individual blood cell telomere attrition rate is telomere length dependent. PLoS Genetics 5, e1000375.CrossRefGoogle ScholarPubMed
Ohlin, B, Nilsson, PM, Nilsson, JA, Berglund, G (2004). Chronic psychosocial stress predicts long-term cardiovascular morbidity and mortality in middle-aged men. European Heart Journal 25, 867873.CrossRefGoogle ScholarPubMed
Pinheiro, J, Bates, D, DebRoy, S, Sarkar, D (2012). nlme: Linear and Nonlinear Mixed Effects Models R package version 3.1–105.Google Scholar
Pinto-Sietsma, SJ, Janssen, WM, Hillege, HL, Navis, G, de, ZD, de Jong, PE (2000). Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population. Journal of the American Society of Nephrology 11, 18821888.CrossRefGoogle Scholar
Price, LH, Kao, HT, Burgers, DE, Carpenter, LL, Tyrka, AR (2012). Telomeres and early-life stress: an overview. Biological Psychiatry 73, 1523.CrossRefGoogle ScholarPubMed
Puterman, E, Lin, J, Krauss, J, Blackburn, EH, Epel, ES (2015). Determinants of telomere attrition over 1 year in healthy older women: stress and health behaviors matter. Molecular Psychiatry 20, 529535.CrossRefGoogle ScholarPubMed
R Foundation for Statistical Computing (2012). R: A Language and Environment for Statistical Computing.Google Scholar
Rosengren, A, Hawken, S, Ounpuu, S, Sliwa, K, Zubaid, M, Almahmeed, WA, Blackett, KN, Sitthi-Amorn, C, Sato, H, Yusuf, S (2004). Association of psychosocial risk factors with risk of acute myocardial infarction in 11119 cases and 13648 controls from 52 countries (the INTERHEART study): case-control study. Lancet 364, 953962.CrossRefGoogle ScholarPubMed
Rosmalen, JGM, Bos, EH, de Jonge, P (2012). Validation of the Long-term Difficulties Inventory (LDI) and the List of Threatening Experiences (LTE) as measures of stress in epidemiological population-based cohort studies. Psychological Medicine 42, 25992608.CrossRefGoogle ScholarPubMed
Segerstrom, SC, Miller, GE (2004). Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychological Bulletin 130, 601630.CrossRefGoogle ScholarPubMed
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. Molecular Psychiatry 18, 576581.CrossRefGoogle ScholarPubMed
Steenstrup, T, Hjelmborg, JV, Kark, JD, Christensen, K, Aviv, A (2013). The telomere lengthening conundrum--artifact or biology? Nucleic Acids Research 41, e131.CrossRefGoogle ScholarPubMed
Steptoe, A, Hamer, M, Butcher, L, Lin, J, Brydon, L, Kivimaki, M, Marmot, M, Blackburn, E, Erusalimsky, JD (2011). Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women. Brain, Behavior, and Immunity 25, 12921298.CrossRefGoogle Scholar
Steptoe, A, Hamer, M, Chida, Y (2007). The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain, Behavior, and Immunity 21, 901912.CrossRefGoogle ScholarPubMed
Svenson, U, Nordfjall, K, Baird, D, Roger, L, Osterman, P, Hellenius, ML, Roos, G (2011). Blood cell telomere length is a dynamic feature. PloS ONE 6, e21485.CrossRefGoogle ScholarPubMed
Takubo, K, Izumiyama-Shimomura, N, Honma, N, Sawabe, M, Arai, T, Kato, M, Oshimura, M, Nakamura, K (2002). Telomere lengths are characteristic in each human individual. Experimental Gerontology 37, 523531.CrossRefGoogle ScholarPubMed
Valdes, AM, Andrew, T, Gardner, JP, Kimura, M, Oelsner, E, Cherkas, LF, Aviv, A, Spector, TD (2005). Obesity, cigarette smoking, and telomere length in women. Lancet 366, 662664.CrossRefGoogle ScholarPubMed
van Ockenburg, SL, de Jonge, P, van der Harst, P, Ormel, J, Rosmalen, JG (2014). Does neuroticism make you old? Prospective associations between neuroticism and leukocyte telomere length. Psychological Medicine, 44, 723729.CrossRefGoogle ScholarPubMed
Vickers, AJ, Altman, DG (2001). Statistics notes: analysing controlled trials with baseline and follow up measurements. BMJ (Clinical Research ed.) 323, 11231124.CrossRefGoogle ScholarPubMed
Willeit, P, Willeit, J, Mayr, A, Weger, S, Oberhollenzer, F, Brandstatter, A, Kronenberg, F, Kiechl, S (2010). Telomere length and risk of incident cancer and cancer mortality. Journal of the American Medical Association 304, 6975.CrossRefGoogle ScholarPubMed
Wolkowitz, OM, Mellon, SH, Epel, ES, Lin, J, Reus, VI, Rosser, R, Burke, H, Compagnone, M, Nelson, JC, Dhabhar, FS, Blackburn, EH (2012). Resting leukocyte telomerase activity is elevated in major depression and predicts treatment response. Molecular Psychiatry 17, 164172.CrossRefGoogle ScholarPubMed