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The Relationship between All-Cause Natural Mortality and Copy Number of Mitochondrial DNA in a 15-Year Follow-Up Study

Malyutina, Sofia; Maximov, Vladimir; Chervova, Olga; Orlov, Pavel; Ivanova, Anastasiya; Mazdorova, Ekaterina; Ryabikov, Andrew; ... Voevoda, Mikhail; + view all (2023) The Relationship between All-Cause Natural Mortality and Copy Number of Mitochondrial DNA in a 15-Year Follow-Up Study. International Journal of Molecular Sciences , 24 (13) , Article 10469. 10.3390/ijms241310469. Green open access

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Abstract

We explored the relationship between the copy number of mitochondrial DNA (mtDNA-CN) and all-cause natural mortality. We examined a random population sample in 2003/2005 (n = 9360, men/women, 45–69, the HAPIEE project) and followed up for 15 years. Using a nested case–control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer (n = 371), and a sex- and age-stratified control (n = 785). The odds ratios (ORs) of death were 1.06 (95%CI 1.01–1.11) per one-decile decrease in mtDNA-CN independent of age, sex, metabolic factors, smoking, alcohol intake and education. The age–sex-adjusted ORs of death in the second and first tertiles of mtDNA-CN vs. the top tertile were 2.35 (95% CI 1.70–3.26) and 1.59 (1.16–2.17); an increased risk was confined to the second tertile after controlling for smoking and metabolic factors. The multivariable-adjusted OR of CVD death was 1.92 (95% CI 1.18–3.15) in tertile 2 vs. the top tertile of mtDNA-CN, and for cancer-related death the ORs were 3.66 (95% CI 2.21–6.05) and 2.29 (95% CI 1.43–3.68) in tertiles 2 and 1 vs. the top tertile. In the Siberian population cohort, the mtDNA-CN was an inverse predictor of the 15-year risk of natural mortality, due to the greatest impact of CVD and cancer-related death. The findings merit attention for exploring further the role of mtDNA in human ageing and the diversity of mortality.

Type: Article
Title: The Relationship between All-Cause Natural Mortality and Copy Number of Mitochondrial DNA in a 15-Year Follow-Up Study
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms241310469
Publisher version: https://doi.org/10.3390/ijms241310469
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Mitochondrial DNA copy number (mtDNA-CN); ageing; mortality; circulatory system diseases; cancer; case–control; population
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10172587
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