Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women

Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and disease risk in obese individuals.

[1]  R. Zee,et al.  Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study. , 2010, Translational research : the journal of laboratory and clinical medicine.

[2]  C. Irwin,et al.  Differentiation of human CD8 T cells: implications for in vivo persistence of CD8+ CD28- cytotoxic effector clones. , 1999, International immunology.

[3]  Camellia P. Clark,et al.  Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects , 2003, Brain, Behavior, and Immunity.

[4]  E. Blackburn,et al.  Telomeres and telomerase: their mechanisms of action and the effects of altering their functions , 2005, FEBS letters.

[5]  R. Effros,et al.  Decline in CD28+ T cells in centenarians and in long-term T cell cultures: A possible cause for both in vivo and in vitro immunosenescence , 1994, Experimental Gerontology.

[6]  Ngianga-Bakwin Kandala,et al.  Meta-analysis of short sleep duration and obesity in children and adults. , 2008, Sleep.

[7]  Paula G. Williams,et al.  Cellular aging and restorative processes: subjective sleep quality and duration moderate the association between age and telomere length in a sample of middle-aged and older adults. , 2014, Sleep.

[8]  Daniel J Buysse,et al.  Self-reported sleep quality is associated with the metabolic syndrome. , 2007, Sleep.

[9]  P. O’Reilly,et al.  Identification of seven loci affecting mean telomere length and their association with disease , 2013, Nature Genetics.

[10]  Daniel J. Buysse,et al.  Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults , 2009, Biological Psychology.

[11]  E. Epel,et al.  Determinants of telomere attrition over one year in healthy older women: Stress and health behaviors matter , 2014, Molecular Psychiatry.

[12]  R. Kronmal,et al.  Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. , 2006, American journal of epidemiology.

[13]  O. Wolkowitz,et al.  Does cellular aging relate to patterns of allostasis? An e`xamination of basal and stress reactive HPA axis activity and telomere length , 2012, Physiology & Behavior.

[14]  A. Starkweather,et al.  An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research , 2014, Nursing research.

[15]  G. Beccuti,et al.  Sleep and obesity , 2011, Current opinion in clinical nutrition and metabolic care.

[16]  F. Cappuccio,et al.  Quantity and Quality of Sleep and Incidence of Type 2 Diabetes A systematic review and meta-analysis , 2010 .

[17]  E. Epel,et al.  Accelerated telomere shortening in response to life stress. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  F. Cappuccio,et al.  Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. , 2010, Sleep.

[19]  Jiali Han,et al.  Associations between Rotating Night Shifts, Sleep Duration, and Telomere Length in Women , 2011, PloS one.

[20]  A. Tomiyama,et al.  Shorter Leukocyte Telomere Length in Midlife Women with Poor Sleep Quality , 2011, Journal of aging research.

[21]  R. Effros,et al.  The role of CD8+ T‐cell replicative senescence in human aging , 2005, Discovery medicine.

[22]  O. Wolkowitz,et al.  Stress and telomere biology: A lifespan perspective , 2013, Psychoneuroendocrinology.

[23]  R. Cawthon Telomere measurement by quantitative PCR. , 2002, Nucleic acids research.

[24]  E. Blackburn,et al.  Short Leukocyte Telomere Length Predicts Risk of Diabetes in American Indians: the Strong Heart Family Study , 2013, Diabetes.

[25]  Daniel J Buysse,et al.  The Pittsburgh sleep quality index: A new instrument for psychiatric practice and research , 1989, Psychiatry Research.

[26]  T. Kamarck,et al.  A global measure of perceived stress. , 1983, Journal of health and social behavior.

[27]  L. Gallicchio,et al.  Sleep duration and mortality: a systematic review and meta‐analysis , 2009, Journal of sleep research.

[28]  Candyce Kroenke,et al.  Analyses and comparisons of telomerase activity and telomere length in human T and B cells: insights for epidemiology of telomere maintenance. , 2010, Journal of immunological methods.

[29]  H. Brenner,et al.  Body mass index and leukocyte telomere length in adults: a systematic review and meta‐analysis , 2014, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[30]  P. Berggren,et al.  Short Telomeres Compromise β-Cell Signaling and Survival , 2011, PloS one.

[31]  A. Steptoe,et al.  Short Sleep Duration Is Associated with Shorter Telomere Length in Healthy Men: Findings from the Whitehall II Cohort Study , 2012, PloS one.

[32]  J. Manson,et al.  A prospective study of self-reported sleep duration and incident diabetes in women. , 2003, Diabetes care.

[33]  Frank H. Wilhelm,et al.  Cell aging in relation to stress arousal and cardiovascular disease risk factors , 2006, Psychoneuroendocrinology.

[34]  I. Gurubhagavatula,et al.  Habitual sleep duration associated with self-reported and objectively determined cardiometabolic risk factors. , 2014, Sleep medicine.

[35]  E. Epel,et al.  Obesity and Immunosenescence: Psychological, Behavioral and Biochemical Pathways , 2013 .

[36]  E. Epel,et al.  Poor sleep quality potentiates stress-induced cytokine reactivity in postmenopausal women with high visceral abdominal adiposity , 2014, Brain, Behavior, and Immunity.

[37]  V A Zakian,et al.  Structure and function of telomeres. , 1989, Annual review of genetics.

[38]  O. Wolkowitz,et al.  Dysregulated physiological stress systems and accelerated cellular aging , 2014, Neurobiology of Aging.

[39]  J. Eriksson,et al.  The history of sleep apnea is associated with shorter leukocyte telomere length: the Helsinki Birth Cohort Study. , 2014, Sleep medicine.

[40]  R. Effros,et al.  Reduced telomerase activity in human T lymphocytes exposed to cortisol , 2008, Brain, Behavior, and Immunity.

[41]  C. Franceschi,et al.  Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[42]  M. Walker,et al.  The human emotional brain without sleep — a prefrontal amygdala disconnect , 2007, Current Biology.

[43]  K. Strohl,et al.  Using the Berlin Questionnaire To Identify Patients at Risk for the Sleep Apnea Syndrome , 1999, Annals of Internal Medicine.

[44]  Nancy E. Adler,et al.  The rate of leukocyte telomere shortening predicts mortality from cardiovascular disease in elderly men , 2008, Aging.

[45]  R. Effros,et al.  T cell replicative senescence in human aging. , 2013, Current pharmaceutical design.

[46]  S. Manuck,et al.  Stress, immune reactivity and susceptibility to infectious disease , 2002, Physiology & Behavior.

[47]  Stephen Kaptoge,et al.  Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis , 2014, BMJ : British Medical Journal.

[48]  John Trinder,et al.  Sick and tired: does sleep have a vital role in the immune system? , 2004, Nature Reviews Immunology.

[49]  K. Junghanns,et al.  Sleep disturbances are correlated with decreased morning awakening salivary cortisol , 2004, Psychoneuroendocrinology.

[50]  Daniel J Buysse,et al.  Self-reported sleep duration is associated with the metabolic syndrome in midlife adults. , 2008, Sleep.

[51]  P. McDonald,et al.  Brain, Behavior and Immunity in Cancer , 2008 .

[52]  P. Gehrman,et al.  Sleep disturbance is associated with cardiovascular and metabolic disorders , 2012, Journal of sleep research.

[53]  L. Chin,et al.  Telomere dysfunction induces metabolic and mitochondrial compromise , 2011, Nature.

[54]  B. Johansson,et al.  Expansions of peripheral blood CD8 T-lymphocyte subpopulations and an association with cytomegalovirus seropositivity in the elderly: the Swedish NONA immune study , 2002, Experimental Gerontology.

[55]  R. Eckel,et al.  Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain , 2013, Proceedings of the National Academy of Sciences.

[56]  Andrew F. Hayes,et al.  Computational procedures for probing interactions in OLS and logistic regression: SPSS and SAS implementations , 2009, Behavior research methods.

[57]  R. Effros Kleemeier Award Lecture 2008--the canary in the coal mine: telomeres and human healthspan. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[58]  J S Yudkin,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society Subcutaneous Adipose Tissue Releases Interleukin-6, But Not Tumor Necrosis Factor-�, in Vivo* , 2022 .

[59]  T. Stulnig,et al.  Obesity, Inflammation, and Insulin Resistance – A Mini-Review , 2009, Gerontology.

[60]  K. Walsh,et al.  Adipokines in inflammation and metabolic disease , 2011, Nature Reviews Immunology.

[61]  S. Rubin,et al.  Cumulative Inflammatory Load Is Associated with Short Leukocyte Telomere Length in the Health, Aging and Body Composition Study , 2011, PloS one.

[62]  R. Effros,et al.  Immunosenescence: what does it mean to health outcomes in older adults? , 2009, Current opinion in immunology.

[63]  Daniel J Buysse Sleep health: can we define it? Does it matter? , 2014, Sleep.

[64]  T. Kamarck,et al.  Exaggerated Blood Pressure Responses During Mental Stress Are Prospectively Related to Enhanced Carotid Atherosclerosis in Middle-Aged Finnish Men , 2004, Circulation.

[65]  C. Guilleminault,et al.  Meta-analysis of quantitative sleep parameters from childhood to old age in healthy individuals: developing normative sleep values across the human lifespan. , 2004, Sleep.

[66]  Andrew G Rundle,et al.  Sleep duration as a risk factor for diabetes incidence in a large U.S. sample. , 2007, Sleep.

[67]  E. Epel,et al.  An intricate dance: Life experience, multisystem resiliency, and rate of telomere decline throughout the lifespan. , 2012, Social and personality psychology compass.

[68]  O. Wolkowitz,et al.  Major depressive disorder and accelerated cellular aging: results from a large psychiatric cohort study , 2014, Molecular Psychiatry.

[69]  J. Mullington,et al.  Sleep, inflammation and cardiovascular disease. , 2012, Frontiers in bioscience.

[70]  Siobhan Banks,et al.  Sleep deprivation and stressors: evidence for elevated negative affect in response to mild stressors when sleep deprived. , 2012, Emotion.

[71]  Daniel J Buysse,et al.  Validation of a 3-factor scoring model for the Pittsburgh sleep quality index in older adults. , 2006, Sleep.

[72]  E. Epel,et al.  Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. , 2013, JAMA.

[73]  Kathryn A. Lee,et al.  Telomere length is associated with sleep duration but not sleep quality in adults with human immunodeficiency virus. , 2014, Sleep.