Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Nutrients. 2024 May 8;16(10):1417. doi: 10.3390/nu16101417.
The aim of this study was to assess the causal relationships between mineral metabolism disorders, representative of trace elements, and key aging biomarkers: telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN). Utilizing bidirectional Mendelian randomization (MR) analysis in combination with the two-stage least squares (2SLS) method, we explored the causal relationships between mineral metabolism disorders and these aging indicators. Sensitivity analysis can be used to determine the reliability and robustness of the research results. The results confirmed that a positive causal relationship was observed between mineral metabolism disorders and TL ( < 0.05), while the causal relationship with mtDNA-CN was not significant ( > 0.05). Focusing on subgroup analyses of specific minerals, our findings indicated a distinct positive causal relationship between iron metabolism disorders and both TL and mtDNA-CN ( < 0.05). In contrast, disorders in magnesium and phosphorus metabolism did not exhibit significant causal effects on either aging biomarker ( > 0.05). Moreover, reverse MR analysis did not reveal any significant causal effects of TL and mtDNA-CN on mineral metabolism disorders ( > 0.05). The combination of 2SLS with MR analysis further reinforced the positive causal relationship between iron levels and both TL and mtDNA-CN ( < 0.05). Notably, the sensitivity analysis did not indicate significant pleiotropy or heterogeneity within these causal relationships ( > 0.05). These findings highlight the pivotal role of iron metabolism in cellular aging, particularly in regulating TL and sustaining mtDNA-CN, offering new insights into how mineral metabolism disorders influence aging biomarkers. Our research underscores the importance of trace element balance, especially regarding iron intake, in combating the aging process. This provides a potential strategy for slowing aging through the adjustment of trace element intake, laying the groundwork for future research into the relationship between trace elements and healthy aging.
本研究旨在评估矿物质代谢紊乱与关键衰老生物标志物（端粒长度（TL）和线粒体 DNA 拷贝数（mtDNA-CN））之间的因果关系。我们采用双向孟德尔随机化（MR）分析结合两阶段最小二乘法（2SLS）方法，探讨了矿物质代谢紊乱与这些衰老指标之间的因果关系。敏感性分析可用于确定研究结果的可靠性和稳健性。结果证实，矿物质代谢紊乱与 TL 之间存在正因果关系（<0.05），而与 mtDNA-CN 之间的因果关系不显著（>0.05）。在特定矿物质的亚组分析中，我们发现铁代谢紊乱与 TL 和 mtDNA-CN 之间存在明显的正因果关系（<0.05）。相比之下，镁和磷代谢紊乱对这两个衰老标志物均无显著的因果效应（>0.05）。此外，反向 MR 分析未发现 TL 和 mtDNA-CN 对矿物质代谢紊乱有任何显著的因果效应（>0.05）。2SLS 与 MR 分析的结合进一步证实了铁水平与 TL 和 mtDNA-CN 之间的正因果关系（<0.05）。值得注意的是，敏感性分析未表明这些因果关系中存在显著的多效性或异质性（>0.05）。这些发现强调了铁代谢在细胞衰老中的关键作用，特别是在调节 TL 和维持 mtDNA-CN 方面，为矿物质代谢紊乱如何影响衰老标志物提供了新的见解。我们的研究强调了微量元素平衡的重要性，尤其是铁的摄入，这为通过调整微量元素摄入来延缓衰老提供了潜在策略，为未来研究微量元素与健康衰老之间的关系奠定了基础。
