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Eur J Epidemiol. 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.

Hang D1,2, Nan H3,4, Kværner AS1,5, De Vivo I6,7, Chan AT7,8, Hu Z2, Shen H2, Giovannucci E9,10,11, Song M12,13.

Author information

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.

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

PMID:
29619669
DOI:
10.1007/s10654-018-0382-z
[Indexed for MEDLINE]

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