Marij Gielen1, Geja J Hageman2, Evangelia E Antoniou3, Katarina Nordfjall4, Massimo Mangino5,6, Muthuswamy Balasubramanyam7, Tim de Meyer8, Audrey E Hendricks9,10, Erik J Giltay11, Steven C Hunt12, Jennifer A Nettleton13, Klelia D Salpea14, Vanessa A Diaz15, Ramin Farzaneh-Far16, Gil Atzmon17, Sarah E Harris18, Lifang Hou19, David Gilley20, Iiris Hovatta21,22, Jeremy D Kark23, Hisham Nassar24, David J Kurz25, Karen A Mather26, Peter Willeit27, Yun-Ling Zheng28, Sofia Pavanello29, Ellen W Demerath30, Line Rode31, Daniel Bunout32, Andrew Steptoe33, Lisa Boardman34, Amelia Marti35,36,37, Belinda Needham38, Wei Zheng39, Rosalind Ramsey-Goldman40, Andrew J Pellatt41, Jaakko Kaprio42,43, Jonathan N Hofmann44, Christian Gieger45, Giuseppe Paolisso46, Jacob B H Hjelmborg47, Lisa Mirabello46, Teresa Seeman48, Jason Wong49, Pim van der Harst50, Linda Broer51, Florian Kronenberg52, Barbara Kollerits52, Timo Strandberg53, Dan T A Eisenberg54, Catherine Duggan55, Josine E Verhoeven56, Roxanne Schaakxs56, Raffaela Zannolli57, Rosana M R Dos Reis58, Fadi J Charchar59, Maciej Tomaszewski60,61, Ute Mons62,63, Ilja Demuth64, Andrea Elena Iglesias Molli65, Guo Cheng66, Dmytro Krasnienkov67, Bianca D'Antono68, Marek Kasielski69, Barry J McDonnell70, Richard Paul Ebstein71, Kristina Sundquist72, Guillaume Pare73, Michael Chong73, Maurice P Zeegers1,74. 1. Departments of Complex Genetics. 2. Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht University, Netherlands. 3. Department of Clinical Psychological Science, Faculty of Psychology and Neuroscience, Maastricht University, Netherlands. 4. Department of Medicine, Östersund Hospital, Östersund, Sweden. 5. Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. 6. NIHR Biomedical Research Center at Guy's and St. Thomas' Foundation Trust, London, United Kingdom. 7. Cell and Molecular Biology, Madras Diabetes Research Foundation, Gopalapuram, Chennai, India. 8. Department of Mathematical Modeling, Statistics, and Bioinformatics, Ghent University, Ghent, Belgium. 9. Population Sciences Branch of the National Heart, Lung, and Blood Institute (NHLBI), NIH, NHLBI's Framingham Heart Study, Framingham, MA. 10. Department of Mathematical and Statistical Sciences, University of Colorado-Denver, Denver, CO. 11. Department of Psychiatry, Leiden University Medical Center, Leiden, Netherlands. 12. Cardiovascular Genetics Division, Department of Medicine, University of Utah, Salt Lake City, UT. 13. Division of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center, Houston, TX. 14. Department of Molecular Biology and Genetics, BSRC "Alexander Fleming," Athens, Greece. 15. Department of Family Medicine, Medical University of South Carolina, Charleston, SC. 16. Division of Cardiology, San Francisco General Hospital, San Francisco, CA. 17. Department of Medicine and Genetics, Albert Einstein College of Medicine, Bronx, NY, and Department of Biology, Faculty of Natural Science, University of Haifa, Haifa, Israel. 18. Center for Cognitive Aging and Cognitive Epidemiology and Medical Genetics Section and Center for Genomics and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom. 19. Department of Preventive Medicine and Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL. 20. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN. 21. Department of Biosciences, University of Helsinki, Helsinki, Finland. 22. Department of Health, National Institute for Health and Welfare, Helsinki, Finland. 23. Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel. 24. Department of Cardiology, Hadassah University Medical Center, Jerusalem, Israel. 25. Department of Cardiology, Triemli Hospital, Zurich, Switzerland. 26. Centre for Healthy Brain Ageing, Psychiatry, UNSW Australia, Sydney, Australia. 27. Department of Neurology, Medical University Innsbruck, Innsbruck, Austria, and Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom. 28. Department of Oncology, Georgetown University Medical Center, Georgetown University, Washington, DC. 29. Department of Cardiac, Thoracic, and Vascular Sciences, Unit of Occupational Medicine, University of Padova, Padova, Italy. 30. Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN. 31. The Copenhagen General Population Study, Department of Clinical Biochemistry, Copenhagen University Hospital, Herlev and Gentofte Hospital, Copenhagen, Denmark. 32. Institute of Nutrition and Food Technology University of Chile, Santiago, Chile. 33. Department of Epidemiology and Public Health, University College London, London, United Kingdom. 34. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN. 35. Department of Nutrition, Food Science, and Physiology, University of Navarra, Pamplona, Spain. 36. Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain. 37. CIBER Fisiopatología de la Obesidad y Nutrición, (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain. 38. Department of Epidemiology, University of Michigan, Ann Arbor, MI. 39. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN. 40. Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL. 41. Department of Medicine, University of Utah, Salt Lake City, UT. 42. Department of Public Health. 43. Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland. 44. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD. 45. Research Unit of Molecular Epidemiology and Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany. 46. Department of Medical, Surgical, Neurological, Metabolic, and Geriatric Sciences, Second University of Naples, Naples, Italy. 47. Department of Epidemiology, Biostatistics, and Biodemography, Institute of Public Health, University of Southern Denmark, Odense C, Denmark. 48. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA. 49. Stanford University School of Medicine, Stanford, CA. 50. Department of Cardiology, University Medical Center Groningen, Groningen, Netherlands. 51. Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands. 52. Division of Genetic Epidemiology, Department of Medical Genetics, Molecular, and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria. 53. University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Center for Life Course Epidemiology, University of Oulu, Oulu, Finland. 54. Department of Anthropology and Center for Studies in Demography and Ecology, University of Washington, Seattle, WA. 55. The Fred Hutchinson Cancer Research Center, Seattle, WA. 56. Department of Psychiatry, VU University Medical Center, Amsterdam Public Health Research Institute, Amsterdam, Netherlands. 57. Pediatrics Unit, Azienda Ospedaliera Universitaria, Senese/University of Siena, Policlinico Le Scotte, Siena, Italy. 58. Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. 59. School of Science and Technology, Federation University Australia, Department of Physiology, University of Melbourne, Melbourne, Australia, and Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom. 60. Division of Cardiovascular Sciences, Faculty of Medicine, Biology, and Health, University of Manchester, Manchester, United Kingdom. 61. Division of Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom. 62. Division of Clinical Epidemiology and Aging Research. 63. Cancer Prevention Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. 64. Charité-Universitätsmedizin Berlin (corporate member of Freie Universität Berlin), Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Berlin, Germany. 65. CONICET-Universidad de Buenos Aires. Instituto de Inmunología, Genética y Metabolismo (INIGEM). Laboratorio de Diabetes y Metabolismo, Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina. 66. Department of Nutrition, Food Safety, and Toxicology, West China School of Public Health, Sichuan University, Chengdu, China. 67. Department of Epigenetics, DF Chebotarev State Institute of Gerontology NAMS of Ukraine, Kyiv, Ukraine. 68. Research Center, Montreal Heart Institute, and Psychology Department, University of Montreal, Montreal, Quebec, Canada. 69. Bases of Clinical Medicine Teaching Center, Medical University of Lodz, Lodz, Poland. 70. Cardiff School of Sport and Health Sciences, Cardiff Metropolitan University, Cardiff, United Kingdom. 71. Department of Psychology, National University of Singapore, Singapore. 72. Center for Primary Health Care Research, Lund University, Region Skåne, Lund, Sweden. 73. Population Health Research Institute and McMaster University, Hamilton, Canada. 74. CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, Netherlands.
Abstract
Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.
Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obesepersons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.
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