Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

doi:10.1007/s10654-018-0382-z

. 2018 May;33(5):485-495.

doi: 10.1007/s10654-018-0382-z. Epub 2018 Apr 4.

Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

Dong Hang^{1

2}, Hongmei Nan^{3

4}, Ane Sørlie Kværner^{1

5}, Immaculata De Vivo^{6

7}, Andrew Tan Chan^{7

8}, Zhibin Hu², Hongbing Shen², Edward Giovannucci^{9

10

11}, Mingyang Song^{12

13}

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA.
² Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
⁴ Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
⁵ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Room 906, 55 Fruit Street, Boston, MA, 02114, USA.
⁹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA. egiovann@hsph.harvard.edu.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. egiovann@hsph.harvard.edu.
¹¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. egiovann@hsph.harvard.edu.
¹² Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA. msong2@mgh.harvard.edu.
¹³ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Room 906, 55 Fruit Street, Boston, MA, 02114, USA. msong2@mgh.harvard.edu.

PMID: 29619669
PMCID: PMC8063494
DOI: 10.1007/s10654-018-0382-z

Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

Dong Hang et al. Eur J Epidemiol. 2018 May.

. 2018 May;33(5):485-495.

doi: 10.1007/s10654-018-0382-z. Epub 2018 Apr 4.

Authors

Affiliations

¹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA.
² Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA.
⁴ Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
⁵ Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
⁶ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁸ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Room 906, 55 Fruit Street, Boston, MA, 02114, USA.
⁹ Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA. egiovann@hsph.harvard.edu.
¹⁰ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. egiovann@hsph.harvard.edu.
¹¹ Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. egiovann@hsph.harvard.edu.
¹² Department of Nutrition, Harvard T.H. Chan School of Public Health, Room 371, Bldg. 2, 665 Huntington Avenue, Boston, MA, 02115, USA. msong2@mgh.harvard.edu.
¹³ Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Room 906, 55 Fruit Street, Boston, MA, 02114, USA. msong2@mgh.harvard.edu.

PMID: 29619669
PMCID: PMC8063494
DOI: 10.1007/s10654-018-0382-z

Abstract

Adiposity may cause adverse health outcomes by increasing oxidative stress and systemic inflammation, which can be reflected by altered telomere length (TL) and mitochondrial DNA copy number (mtCN) in peripheral blood leukocytes. However, little is known about the influence of lifetime adiposity on TL and mtCN in later life. This study was performed to investigate the associations of lifetime adiposity with leukocyte TL and mtCN in 9613 participants from the Nurses' Health Study. A group-based trajectory modelling approach was used to create trajectories of body shape from age 5 through 60 years, and a genetic risk score (GRS) was created based on 97 known adiposity susceptibility variants. Associations of body shape trajectories and GRS with dichotomized TL and mtCN were assessed by logistic regression models. After adjustment for lifestyle and dietary factors, compared with the lean-stable group, the lean-marked increase group had higher odds of having below-median TL (OR = 1.18, 95% CI 1.04, 1.35; P = 0.01), and the medium-marked increase group had higher odds of having below-median mtCN (OR = 1.28, 95% CI 1.00, 1.64; P = 0.047). There was a suggestive trend toward lower mtCN across the GRS quartiles (P for trend = 0.07). In conclusion, telomere attrition may be accelerated by marked weight gain in middle life, whereas mtCN is likely to be reduced persistently by adiposity over the life course. The findings indicate the importance of lifetime weight management to preserve functional telomeres and mitochondria.

Keywords: Adiposity; Genetic variants; Mitochondrion; Telomere; Trajectory analysis.

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Conflict of interest statement

Competing interests

The authors declare that they have no conflict of interest.

Figures

**Fig. 1**
Trajectories of body shape by age among 9613 women in the Nurses’ Health Study. Mean body mass index at age 60 is shown for each trajectory group

See this image and copyright information in PMC

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References

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[1] Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804–814. - PubMed

[2] Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804–814. - PubMed

[3] Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–781. - PMC - PubMed

[4] Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, Abraham JP, Abu-Rmeileh NM, Achoki T, AlBuhairan FS, Alemu ZA, Alfonso R, Ali MK, Ali R, Guzman NA, Ammar W, Anwari P, Banerjee A, Barquera S, Basu S, Bennett DA, Bhutta Z, Blore J, Cabral N, Nonato IC, Chang JC, Chowdhury R, Courville KJ, Criqui MH, Cundiff DK, Dabhadkar KC, Dandona L, Davis A, Dayama A, Dharmaratne SD, Ding EL, Durrani AM, Esteghamati A, Farzadfar F, Fay DF, Feigin VL, Flaxman A, Forouzanfar MH, Goto A, Green MA, Gupta R, Hafezi-Nejad N, Hankey GJ, Harewood HC, Havmoeller R, Hay S, Hernandez L, Husseini A, Idrisov BT, Ikeda N, Islami F, Jahangir E, Jassal SK, Jee SH, Jeffreys M, Jonas JB, Kabagambe EK, Khalifa SE, Kengne AP, Khader YS, Khang YH, Kim D, Kimokoti RW, Kinge JM, Kokubo Y, Kosen S, Kwan G, Lai T, Leinsalu M, Li Y, Liang X, Liu S, Logroscino G, Lotufo PA, Lu Y, Ma J, Mainoo NK, Mensah GA, Merriman TR, Mokdad AH, Moschandreas J, Naghavi M, Naheed A, Nand D, Narayan KM, Nelson EL, Neuhouser ML, Nisar MI, Ohkubo T, Oti SO, Pedroza A, Prabhakaran D, Roy N, Sampson U, Seo H, Sepanlou SG, Shibuya K, Shiri R, Shiue I, Singh GM, Singh JA, Skirbekk V, Stapelberg NJ, Sturua L, Sykes BL, Tobias M, Tran BX, Trasande L, Toyoshima H, van de Vijver S, Vasankari TJ, Veerman JL, Velasquez-Melendez G, Vlassov VV, Vollset SE, Vos T, Wang C, Wang X, Weiderpass E, Werdecker A, Wright JL, Yang YC, Yatsuya H, Yoon J, Yoon SJ, Zhao Y, Zhou M, Zhu S, Lopez AD, Murray CJ, Gakidou E Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–781. - PMC - PubMed

[5] Heymsfield SB, Wadden TA Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017;376(3):254–266. - PubMed

[6] Heymsfield SB, Wadden TA Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med. 2017;376(3):254–266. - PubMed

[7] Rani V, Deep G, Singh RK, Palle K, Yadav UC Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183–193. - PubMed

[8] Rani V, Deep G, Singh RK, Palle K, Yadav UC Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. Life Sci. 2016;148:183–193. - PubMed

[9] Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med. 2008;44(3):235–246. - PubMed

[10] Houben JM, Moonen HJ, van Schooten FJ, Hageman GJ Telomere length assessment: biomarker of chronic oxidative stress? Free Radic Biol Med. 2008;44(3):235–246. - PubMed

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Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

Affiliations

Longitudinal associations of lifetime adiposity with leukocyte telomere length and mitochondrial DNA copy number

Authors

Affiliations

Abstract

Conflict of interest statement

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Cited by

References

MeSH terms

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LinkOut - more resources

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