Low mitochondrial DNA copy number in peripheral blood mononuclear cells is associated with future mortality risk: a long-term follow-up study from Japan

Objectives: The mitochondrial DNA (mtDNA) is unique and circular with multiple copies of the genome. The lower mtDNA copy number (mtDNA-CN) in leukocytes is associated with the risk of all -cause mortality. However, its longterm association is unknown. Thus, the study examined the association between mtDNA-CN and the risk of all -cause mortality in a long-term follow-up study in the Japanese population. Design: This longitudinal study included the study cohort from an annual, population-based health checkup in the town of Yakumo, Hokkaido, Japan. Setting and Participants: 814 participants (baseline age range: 38-80 years, mean: 56.3 years) were included in this study in 1990. They were followed -up regarding mortality for about 30 years (median: 28.1 years) till 2019. Measures: The genomic DNA was extracted from peripheral blood mononuclear cells and the mtDNA-CN was measured using real-time polymerase chain reaction. The level of the mtDNA-CN was divided into tertiles (low, middle, and high). The participants were categorized based on their age into middle-aged (<60 years old) or oldaged (>= 60 years old). Survival analysis was performed for tertile of mtDNA-CN and compared using the log -rank test. Univariate and multivariable Cox proportional hazard regression analyses were performed to assess the association between mtDNA-CN and all-cause mortality. The model adjusted with age, sex, body mass index, systolic blood pressure, smoking habit, alcohol consumption, exercise habit, and education level. Results: The low levels of mtDNA-CN resulted in a significant decrease in cumulative survival rate (P < 0.05). The risk of mortality was significantly higher in the middle-aged cohort when mtDNA-CN levels were low (hazard ratios [95% confidence intervals]: 1.98 [1.10-3.56]). Conclusion: This study demonstrated that leukocyte mtDNA-CN is associated with future mortality risk. Our study findings may lead to further research on the early prediction of mortality and its underlying mechanisms. (c) 2023 Published by Elsevier Masson SAS on behalf of SERDI Publisher.