Body mass index is negatively associated with telomere length: A collaborative cross-sectional meta-analysis of 87 observational studies

TELOMAAS group

doi:10.1093/ajcn/nqy107

Body mass index is negatively associated with telomere length: A collaborative cross-sectional meta-analysis of 87 observational studies

TELOMAAS group

Department of Human Biology

Research output: Contribution to journal › Article › peer-review

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-sectionalmeta-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. Studyspecific 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 ageand 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 arewarranted.

Original language	English
Pages (from-to)	453-475
Number of pages	23
Journal	American Journal of Clinical Nutrition
Volume	108
Issue number	3
DOIs	https://doi.org/10.1093/ajcn/nqy107
State	Published - 1 Sep 2018

Bibliographical note

Funding Information:
SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman’s Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska Läkaresällskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyväskylä, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE–European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum München– German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community’s Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007-201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfjäll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo–FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar’s work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski’s work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-Württemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study “Sex-and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany” (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universiätsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universität zu Berlin; all located in Berlin, Germany, and University of Lübeck in Lübeck, and University of Tübingen, Germany].

Funding Information:
The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521.

Funding Information:
GAHR2 was supported by grants awarded to Dr. D’Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the Singapore Ministry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the “Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study” conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166).

Funding Information:
The TwinsUK study was funded by the Wellcome Trust, European Community’s Seventh Framework Programme (FP7/2007–2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the US-Israel Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21– 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the “Tiroler Wissenschaftsfonds,” Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252).

Funding Information:
The TwinsUK study was funded by the Wellcome Trust, European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729- 04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the USIsrael Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21- 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the "Tiroler Wissenschaftsfonds," Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252). The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521. SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman's Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska Läkaresällskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyväskylä, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum München- German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007- 201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfjäll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar's work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski's work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-Württemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study "Sex- and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany" (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universiätsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universität zu Berlin; all located in Berlin, Germany, and University of Lübeck in Lübeck, and University of Tübingen, Germany]. This study corresponds to a substudy of "Venado Tuerto 2." The authors thank Hugo Grancelli, Dra Monica Damiano, Daniel Fox, and Carlos Ranalli; the Regional Centre for Development; School of Social Work of Venado Tuerto; Nutrition Society of Venado Tuerto; and the Department of Cardiology Hospital Alejandro Gutierrez of Venado Tuerto for their collaboration. GAHR2 was supported by grants awarded to Dr. D'Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the SingaporeMinistry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the "Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study" conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166).

Publisher Copyright:
© 2018 American Society for Nutrition.

Keywords

BMI
Low-grade inflammation
Meta-analysis
Obesity
Observational studies
Telomere length

ASJC Scopus subject areas

Medicine (miscellaneous)
Nutrition and Dietetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1093/ajcn/nqy107

Cite this

@article{73d676a1997546ac94a84e4196cd9768,

title = "Body mass index is negatively associated with telomere length: A collaborative cross-sectional meta-analysis of 87 observational studies",

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-sectionalmeta-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. Studyspecific 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 ageand 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 arewarranted.",

keywords = "BMI, Low-grade inflammation, Meta-analysis, Obesity, Observational studies, Telomere length",

author = "{TELOMAAS group} and Marij Gielen and Hageman, {Geja J.} and Antoniou, {Evangelia E.} and Katarina Nordfjall and Massimo Mangino and Muthuswamy Balasubramanyam and {De Meyer}, Tim and Hendricks, {Audrey E.} and Giltay, {Erik J.} and Hunt, {Steven C.} and Nettleton, {Jennifer A.} and Salpea, {Klelia D.} and Diaz, {Vanessa A.} and Ramin Farzaneh-Far and Gil Atzmon and Harris, {Sarah E.} and Lifang Hou and David Gilley and Iiris Hovatta and Kark, {Jeremy D.} and Hisham Nassar and Kurz, {David J.} and Mather, {Karen A.} and Peter Willeit and Zheng, {Yun Ling} and Sofia Pavanello and Demerath, {Ellen W.} and Line Rode and Daniel Bunout and Andrew Steptoe and Lisa Boardman and Amelia Marti and Belinda Needham and Wei Zheng and Rosalind Ramsey-Goldman and Pellatt, {Andrew J.} and Jaakko Kaprio and Hofmann, {Jonathan N.} and Christian Gieger and Giuseppe Paolisso and Hjelmborg, {Jacob B.H.} and Lisa Mirabello and Teresa Seeman and Jason Wong and {Van Der Harst}, Pim and Linda Broer and Florian Kronenberg and Barbara Kollerits and Timo Strandberg and Eisenberg, {Dan T.A.}",

note = "Funding Information: SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman{\textquoteright}s Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska L{\"a}kares{\"a}llskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyv{\"a}skyl{\"a}, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE–European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum M{\"u}nchen– German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universit{\"a}t, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007-201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfj{\"a}ll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the S{\~a}o Paulo Research Foundation (Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo–FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar{\textquoteright}s work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski{\textquoteright}s work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-W{\"u}rttemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study “Sex-and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany” (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universi{\"a}tsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universit{\"a}t zu Berlin; all located in Berlin, Germany, and University of L{\"u}beck in L{\"u}beck, and University of T{\"u}bingen, Germany]. Funding Information: The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521. Funding Information: GAHR2 was supported by grants awarded to Dr. D{\textquoteright}Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the Singapore Ministry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the “Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study” conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166). Funding Information: The TwinsUK study was funded by the Wellcome Trust, European Community{\textquoteright}s Seventh Framework Programme (FP7/2007–2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy{\textquoteright}s and St. Thomas{\textquoteright} NHS Foundation Trust and King{\textquoteright}s College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the US-Israel Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21– 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the “Tiroler Wissenschaftsfonds,” Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252). Funding Information: The TwinsUK study was funded by the Wellcome Trust, European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729- 04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the USIsrael Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21- 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the {"}Tiroler Wissenschaftsfonds,{"} Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252). The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521. SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman's Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska L{\"a}kares{\"a}llskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyv{\"a}skyl{\"a}, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum M{\"u}nchen- German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universit{\"a}t, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007- 201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfj{\"a}ll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the S{\~a}o Paulo Research Foundation (Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo-FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar's work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski's work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-W{\"u}rttemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study {"}Sex- and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany{"} (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universi{\"a}tsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universit{\"a}t zu Berlin; all located in Berlin, Germany, and University of L{\"u}beck in L{\"u}beck, and University of T{\"u}bingen, Germany]. This study corresponds to a substudy of {"}Venado Tuerto 2.{"} The authors thank Hugo Grancelli, Dra Monica Damiano, Daniel Fox, and Carlos Ranalli; the Regional Centre for Development; School of Social Work of Venado Tuerto; Nutrition Society of Venado Tuerto; and the Department of Cardiology Hospital Alejandro Gutierrez of Venado Tuerto for their collaboration. GAHR2 was supported by grants awarded to Dr. D'Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the SingaporeMinistry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the {"}Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study{"} conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166). Publisher Copyright: {\textcopyright} 2018 American Society for Nutrition.",

year = "2018",

month = sep,

day = "1",

doi = "10.1093/ajcn/nqy107",

language = "English",

volume = "108",

pages = "453--475",

journal = "American Journal of Clinical Nutrition",

issn = "0002-9165",

publisher = "American Society for Nutrition",

number = "3",

}

TY - JOUR

T1 - Body mass index is negatively associated with telomere length

T2 - A collaborative cross-sectional meta-analysis of 87 observational studies

AU - TELOMAAS group

AU - Gielen, Marij

AU - Hageman, Geja J.

AU - Antoniou, Evangelia E.

AU - Nordfjall, Katarina

AU - Mangino, Massimo

AU - Balasubramanyam, Muthuswamy

AU - De Meyer, Tim

AU - Hendricks, Audrey E.

AU - Giltay, Erik J.

AU - Hunt, Steven C.

AU - Nettleton, Jennifer A.

AU - Salpea, Klelia D.

AU - Diaz, Vanessa A.

AU - Farzaneh-Far, Ramin

AU - Atzmon, Gil

AU - Harris, Sarah E.

AU - Hou, Lifang

AU - Gilley, David

AU - Hovatta, Iiris

AU - Kark, Jeremy D.

AU - Nassar, Hisham

AU - Kurz, David J.

AU - Mather, Karen A.

AU - Willeit, Peter

AU - Zheng, Yun Ling

AU - Pavanello, Sofia

AU - Demerath, Ellen W.

AU - Rode, Line

AU - Bunout, Daniel

AU - Steptoe, Andrew

AU - Boardman, Lisa

AU - Marti, Amelia

AU - Needham, Belinda

AU - Zheng, Wei

AU - Ramsey-Goldman, Rosalind

AU - Pellatt, Andrew J.

AU - Kaprio, Jaakko

AU - Hofmann, Jonathan N.

AU - Gieger, Christian

AU - Paolisso, Giuseppe

AU - Hjelmborg, Jacob B.H.

AU - Mirabello, Lisa

AU - Seeman, Teresa

AU - Wong, Jason

AU - Van Der Harst, Pim

AU - Broer, Linda

AU - Kronenberg, Florian

AU - Kollerits, Barbara

AU - Strandberg, Timo

AU - Eisenberg, Dan T.A.

N1 - Funding Information: SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman’s Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska Läkaresällskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyväskylä, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE–European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum München– German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community’s Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007-201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfjäll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo–FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar’s work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski’s work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-Württemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study “Sex-and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany” (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universiätsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universität zu Berlin; all located in Berlin, Germany, and University of Lübeck in Lübeck, and University of Tübingen, Germany]. Funding Information: The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521. Funding Information: GAHR2 was supported by grants awarded to Dr. D’Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the Singapore Ministry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the “Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study” conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166). Funding Information: The TwinsUK study was funded by the Wellcome Trust, European Community’s Seventh Framework Programme (FP7/2007–2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729-04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the US-Israel Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21– 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the “Tiroler Wissenschaftsfonds,” Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252). Funding Information: The TwinsUK study was funded by the Wellcome Trust, European Community's Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) BioResource Clinical Research Facility and Biomedical Research Centre based at Guy's and St. Thomas' NHS Foundation Trust and King's College London. The Dallas Heart Study (DHS) research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under award number UL1TR001105. We thank Drs. C Garcia and Kozlitina for sharing the data. The acquisition and analyses of the data from the Multi-Ethnic Study of Atherosclerosis (MESA) was funded by contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, by R01 HL076831 (PI: Diez Roux), and by funding from the MacArthur Foundation. Jennifer A Nettleton was funded by a career development award from the NIH, the National Institute of Diabetes and Digestive and Kidney Diseases (5K01DK082729- 04). MESA thanks the investigators, staff, and participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. SE Humphries is a British Heart Foundation Professor and he and Klelia D Salpea are supported by the British Heart Foundation (RG008/08 and FS/06/053) and by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The EARSII study was funded by the EC Concerted Action BMH1 CT92-0206. Phenotype collection was supported by Age UK (The Disconnected Mind project). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, which is part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Counci and Medical Research Council (MRC) is gratefully acknowledged. The Sister Study was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01 ES 044005). The Jerusalem LRC study was funded by the Chief Scientist of the Israel Ministry of Health (300000-5352), the Israel Science Foundation (593/01), and the USIsrael Binational Science Foundation (87-00419). The Jerusalem Palestinians study was funded by the USAID MERC program (grant TA-MOU-01-M21- 002) and by a research grant from DCURE Israel. The PATH study was supported by the Australian National Health and Medical Research Council program grant 17805 and project grant 418020. The Bruneck Study was supported by a grant from the "Tiroler Wissenschaftsfonds," Austria, and the Dr Johannes and Hertha Tuba Foundation. The Fels Longitudinal Study, Research reported in this manuscript was supported by the NIH grants (R03AG023251, R01HD012252). The authors thank the Indian Health Service facilities. The views expressed in this article are those of the authors and do not necessarily reflect those of the Indian Health Service. This study was supported by NIH grants R01DK091369, K01AG034259, R21HL092363, and cooperative agreement grants U01HL65520, U01HL41642, U01HL41652, U01HL41654, and U01HL65521. SOLVABLE was supported by NIH/NIAMS T32AR07611, K24AR002138, and P60 AR30692, which is now updated as P60 AR064464, Kirkland Scholar Award, and the AFMR Summer Clinical and the Eleanor Wood-Prince grant: A Project of the Woman's Board of Northwestern Memorial Hospital. The Former Athletes study was funded by the Ministry of Education and Culture, the Juho Vainio Foundation, the Finnish Heart Research Foundation, Paavo Nurmi Foundation, the Finnish Cultural Foundation, and by a grant from Medical Society of Finland, Finska Läkaresällskapet. We thank National Institute for Health and Welfare, Department of Public Health, University of Helsinki, Sports and Exercise Medicine Department of Health Sciences, University of Jyväskylä, Paavo Nurmi Centre, Turku, and ORTON Research Institute, Invalid Foundation, Helsinki, for collaboration during the large epidemiological and clinical research program in the year 2008. The Finnish Twin Cohort data come primarily from the Nicotine Addictions Genetics family study of twins and their siblings. Data collection for this work was supported by Academy of Finland grants and NIH grant DA12854 (PAFM), and further support was from ENGAGE-European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, grant agreement 201413; the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680; to J Kaprio), and the Academy of Finland (grants 141054, 265240, and 263278; to J Kaprio). The US Kidney Cancer Study (USKCS) was supported, in part, by the intramural research program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH. The KORA study was initiated and financed by the Helmholtz Zentrum München- German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The Erasmus Rucphen Family (ERF) study was supported by grants from The Netherlands Organisation for Scientific Research (NWO), Erasmus MC, the Center for Medical Systems Biology (CMSB), the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE Consortium (grant HEALTH-F4-2007- 201413), and the Netherlands Consortium for Healthy Ageing (grant 050-060-810). We are grateful to all general practitioners for their contributions, to Petra Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work, and Peter Snijders for his help in data collection. The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture, and Sciences; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. The analysis of data from the NHANES was funded by grant R01 AG033592 from the National Institute on Aging (PI: Elissa Epel). The Zutphen Elderly Study was supported by grants from The Netherlands Prevention Foundation (Preventiefonds) and the survey on Crete was financially supported by Danone. The RPCI study was supported by grants from Susan G Komen for the Cure (BCTR 0600562) and the US NIH Cancer Center Support Grant (P30 CA016056). The Heart Scan Study was funded by the British Heart Foundation (RG/10/005/28296) and the Medical Research Council, United Kingdom. A Steptoe is funded by the British Heart Foundation. The Helsinki Businessmen Study (HBS) was initially funded by the Academy of Finland and various foundations during the decades, most recently by the Sohlberg Foundation, the Jahnsson Foundation, and Gustav Voch Victoria Frimurarestiftelse. Funding has also been provided by the Helsinki University Central Hospital, the Oulu University Hospital (VTR/EVO-funding), and the Academy of Finland grants 286294 and 294154. Laboratory analysis of the Cebu Longitudinal Health and Nutrition Survey (CLHNS) was funded by NSF (Doctoral Dissertation Improvement grant BCS-0962282), the Wenner-Gren Foundation (grant 8111), and institutional support from Northwestern University; data and sample collection were funded by the NIH (grants RR20649 and ES10126). DNA extracts were provided by Karen Mohlke. Richard Cawthon, Justin Tackney, Katarina Nordfjäll, Klelia Salpea, Christine Ackerman, and Margrit Urbanek provided laboratory advice. We especially thank the many researchers at the Office of Population Studies, University of San Carlos, Cebu, the Philippines, for their central role in study design and data collection, and the Filipino participants who provided their time and samples for this study. NESDA is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (Zon-Mw, grant 10-000-1002) and is supported by participating universities and mental health care organizations. JE Verhoeven and telomere length assaying were supported through an NWO-VICI grant (91811602). The authors of PRT thank Gislaine Satyko Kogure and Rafael Costa Silva for personal guidance regarding progressive resistance training. We are grateful to the São Paulo Research Foundation (Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP), for financial support with grants 2010/08800-8 and 2012/11566-2 (RMR) and fellowship 2012/11069-9 (CLMF). Fadi Charchar's work was supported by a National Health and Medical Research Council of Australia grant APP1123472. Maciej Tomaszewski's work on the Y chromosome was supported by British Heart Foundation project grants PG/16/49/32176 and PG/12/9/29376. The ESTHER study was funded by the Baden-Württemberg State Ministry of Science, Research, and Arts (Stuttgart, Germany); the Federal Ministry of Education and Research (Berlin, Germany); and the Federal Ministry of Family Affairs, Senior Citizens, Women, and Youth (Berlin, Germany). The Berlin Aging Study II (BASE-II) was supported by the German Federal Ministry of Education and Research (BMBF grants 16SV5536K, 16SV5537, 16SV5538, and 16SV5837; previously 01UW0808)). The study "Sex- and Gender-Sensitive Prevention of Cardiovascular and Metabolic Disease in Older Adults in Germany" (GendAge) includes analyses of BASE-II baseline data and follow-up analyses of BASE-II participants with a focus on sex and gender differences in cardiovascular and metabolic diseases. GendAge is also supported by the BMBF (grants 01GL1716A and 01GL1716B). Additional contributions (e.g., financial, equipment, logistics, personnel) were made from each of the other participating sites [i.e., the Max Planck Institute for Human Development (MPIB); Max Planck Institute for Molecular Genetics (MPIMG); Charite-Universiätsmedizin, University Medicine, German; Institute for Economic Research (DIW) Humboldt-Universität zu Berlin; all located in Berlin, Germany, and University of Lübeck in Lübeck, and University of Tübingen, Germany]. This study corresponds to a substudy of "Venado Tuerto 2." The authors thank Hugo Grancelli, Dra Monica Damiano, Daniel Fox, and Carlos Ranalli; the Regional Centre for Development; School of Social Work of Venado Tuerto; Nutrition Society of Venado Tuerto; and the Department of Cardiology Hospital Alejandro Gutierrez of Venado Tuerto for their collaboration. GAHR2 was supported by grants awarded to Dr. D'Antono by the Canadian Institutes of Health Research (CIHR; MOP 79456 and 111017) and the Montreal Heart Institute Foundation. The RPE study was funded by research grants from the SingaporeMinistry of Education, the AXA Research Foundation, and the Templeton World Charity Foundation, Inc. The Sweden Mindfulness Study was supported by the Swedish Research Council and FORTE to Kristina Sundquist and Jan Sundquist and the National Heart, Lung, and Blood Institute of the NIH under award R01HL116381 to Kristina Sundquist. The Ukrainian part of the data of the Kyev study was completed within the framework of the "Research of anthropometric, biochemical and genetic risk factors of development of the glucose regulation disturbances and diabetes mellitus in Ukraine study" conducted at the Komisarenko Institute of Endocrinology and Metabolism (National Academy of Medical Sciences (grant 0116 U 002166). Publisher Copyright: © 2018 American Society for Nutrition.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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-sectionalmeta-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. Studyspecific 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 ageand 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 arewarranted.

AB - 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-sectionalmeta-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. Studyspecific 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 ageand 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 arewarranted.

KW - BMI

KW - Low-grade inflammation

KW - Meta-analysis

KW - Obesity

KW - Observational studies

KW - Telomere length

UR - http://www.scopus.com/inward/record.url?scp=85054190686&partnerID=8YFLogxK

U2 - 10.1093/ajcn/nqy107

DO - 10.1093/ajcn/nqy107

M3 - Article

C2 - 30535086

AN - SCOPUS:85054190686

SN - 0002-9165

VL - 108

SP - 453

EP - 475

JO - American Journal of Clinical Nutrition

JF - American Journal of Clinical Nutrition

IS - 3

ER -

Body mass index is negatively associated with telomere length: A collaborative cross-sectional meta-analysis of 87 observational studies

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