Papadam Anastasios, Mihov Mihail, Koller Adriana, Weissensteiner Hansi, Stark Klaus, Grassmann Felix
Institute of Medical Science, University of Aberdeen, Aberdeen, UK.
Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Hum Genomics. 2025 Mar 29;19(1):34. doi: 10.1186/s40246-025-00743-8.
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.
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.
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.
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.
线粒体是我们细胞内的小细胞器，对于产生能量和热量、细胞信号传导、重要分子的产生和降解以及细胞死亡至关重要。每个细胞中线粒体的数量是线粒体功能的一个标志，其通常会随着年龄的增长而下降。然而，我们发现线粒体丰度也存在相当大的季节性变化，这值得进一步研究。
我们利用了参与英国生物银行研究的个体的数据，并根据映射到线粒体基因组的外显子测序读数计算了他们的线粒体丰度。将季节效应建模为全年的正弦 - 余弦函数，并通过多变量回归研究了由于各种人口统计学、生活方式、遗传、蛋白质组学和代谢组学标志物导致的线粒体丰度的振幅、峰相位和位移变化。
我们发现冬季的线粒体DNA（mtDNA）丰度高于夏季。这种差异与高龄、较高的体重指数和吸烟行为有关，这些因素导致mtDNA丰度的振幅降低。较高的教育程度降低了峰相位（即，将分布转移到一年中更早的时间），而较高的体重指数和缺乏体育活动导致峰相位延迟。一般来说，免疫细胞计数增加导致振幅降低，而血小板和淋巴细胞计数增加则会增加峰相位。重要的是，季节性振幅降低与心血管、消化、泌尿生殖和呼吸系统疾病以及全因死亡率的风险增加有关。大多数代谢组学和蛋白质组学标志物与mtDNA位移（即基线水平的增加）有关，但与峰相位或振幅无关。同样，我们发现有多个基因变异影响位移，但在研究峰相位或振幅时，没有一个达到全基因组显著性。
mtDNA丰度的季节性变化受环境、生活方式和免疫参数的影响。线粒体丰度季节性振荡的差异可能潜在地解释先前关联结果的差异，并且可能有助于改善未来的风险预测。
