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

• Published in: International journal of molecular sciences 2023-06, Vol.24 (13), p.10469
• Main Authors: Malyutina, Sofia, Maximov, Vladimir, Chervova, Olga, Orlov, Pavel, Ivanova, Anastasiya, Mazdorova, Ekaterina, Ryabikov, Andrew, Simonova, Galina, Voevoda, Mikhail
• Format: Article
• Language: English
• Subjects: ageing; Aging (natural); Cancer; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; case–control; circulatory system diseases; Copy number; Death; DNA Copy Number Variations; DNA methylation; DNA, Mitochondrial - genetics; DNA, Mitochondrial - metabolism; Female; Follow-Up Studies; Genetic research; Health aspects; Humans; Male; Mitochondrial DNA; mitochondrial DNA copy number (mtDNA-CN); Mortality; Multivariable control; Prospective Studies; Risk Factors; Russia; Smoking
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241310469

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 ( = 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 ( = 371), and a sex- and age-stratified control ( = 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.