Tapping natures rhythm: the role of season in mitochondrial function and genetics in the UK biobank.

Abstract

Background: Mitochondria are small organelles inside our cells crucial for producing energy and heat, cell signaling, production and degradation of important molecules, as well as cell death. The number of mitochondria in each cell is a marker for mitochondrial function, which generally declines with increasing age. However, we found that there is also a considerable seasonal variation of mitochondrial abundance, which warrants further research.

Methods: We leveraged data from individuals participating in the UK Biobank study and computed their mitochondrial abundance from Exome sequencing reads mapping to the mitochondrial genome. The seasonal effect was modelled as a sine-cosine function across the year and changes in amplitude, acrophase and displacement of mitochondrial abundance due to various demographic, lifestyle, genetic, proteomic, and metabolomic markers were investigated with multivariate regression.

Results: We found that mitochondrial DNA (mtDNA) abundance was higher in winter than in summer. This difference is related to advanced age, a higher BMI and smoking behavior which resulted in a reduced amplitude of mtDNA abundance. A higher education reduced the acrophase (i.e., shifted the distribution to earlier in the year) and a higher BMI and lack of physical activity led to a later acrophase. Generally, increased immune cell count resulted in lower amplitude, and an increased platelet and lymphocyte count was found to increase the acrophase. Importantly, a reduced seasonal amplitude was associated with increased risk for cardiovascular, digestive, genitourinary, and respiratory diseases as well as all-cause mortality. Most of the metabolomic and proteomic markers were associated with mtDNA displacement (i.e., increase of the baseline level) but not acrophase or amplitude. Similarly, we found that there are multiple genetic variants influencing displacement, but none reached genome-wide significance when investigating acrophase or amplitude.

Conclusion: Seasonal variation of mtDNA abundance is influenced by environmental, lifestyle and immune parameters. Differences in the seasonal oscillation of mitochondrial abundance could potentially explain discrepancies of previous associations results and might be useful to improve future risk prediction.