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European Journal of Epidemiology

, Volume 33, Issue 5, pp 485–495 | Cite as

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

  • Dong Hang
  • Hongmei Nan
  • Ane Sørlie Kværner
  • Immaculata De Vivo
  • Andrew Tan Chan
  • Zhibin Hu
  • Hongbing Shen
  • Edward Giovannucci
  • Mingyang Song
AGEING

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 Telomere Mitochondrion Trajectory analysis Genetic variants 

Notes

Acknowledgements

We would like to thank the participants and staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Authors’ contributions

MS and EG were responsible for study design. DH performed statistical analyses and drafted the manuscript. HN, IV, and AC contributed to acquisition of data. AK, ZH, and HS helped to interpret the results and revised the manuscript critically. All authors read and approved the final manuscript.

Funding

This work was supported by the National Institutes of Health (UM1 CA186107, P01 CA87969, R01 CA49449, R01 HL034594, and R01 HL088521) and by the American Cancer Society Mentored Research Scholar Grant (MRSG-17-220-01 - NEC to M.S.). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10654_2018_382_MOESM1_ESM.docx (539 kb)
Supplementary material 1 (DOCX 539 kb)

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Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Dong Hang
    • 1
    • 2
  • Hongmei Nan
    • 3
    • 4
  • Ane Sørlie Kværner
    • 1
    • 5
  • Immaculata De Vivo
    • 6
    • 7
  • Andrew Tan Chan
    • 7
    • 8
  • Zhibin Hu
    • 2
  • Hongbing Shen
    • 2
  • Edward Giovannucci
    • 1
    • 6
    • 7
  • Mingyang Song
    • 1
    • 8
  1. 1.Department of NutritionHarvard T.H. Chan School of Public HealthBostonUSA
  2. 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 HealthNanjing Medical UniversityNanjingChina
  3. 3.Department of Epidemiology, Richard M. Fairbanks School of Public HealthIndiana UniversityIndianapolisUSA
  4. 4.Indiana University Melvin and Bren Simon Cancer CenterIndianapolisUSA
  5. 5.Department of Nutrition, Institute of Basic Medical SciencesUniversity of OsloOsloNorway
  6. 6.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  7. 7.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  8. 8.Clinical and Translational Epidemiology Unit and Division of GastroenterologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

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