Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study

作者：Zhihao Wang, Yi Liu, Yi Liu, Shuxin Zhang, Yunbo Yuan, Siliang Chen, Wenhao Li, Mingrong Zuo, Yufan Xiang, Tengfei Li, Yuan Yang, Yuan Yang, Yanhui Liu, Yanhui Liu · 发表于：Clinical Epigenetics · 年份：2023 · DOI：10.1186/s13148-023-01575-w · 被引用次数：21 · 研究领域：Epigenetics and DNA Methylation、Hemoglobinopathies and Related Disorders、Iron Metabolism and Disorders

Abstract Background Epigenetic clocks constructed from DNA methylation patterns have emerged as excellent predictors of aging and aging-related health outcomes. Iron, a crucial element, is meticulously regulated within organisms, a phenomenon referred as iron homeostasis. Previous researches have demonstrated the sophisticated connection between aging and iron homeostasis. However, their causal relationship remains relatively unexplored. Results Through two-sample Mendelian randomization (MR) utilizing the random effect inverse variance weighted (IVW) method, each standard deviation (SD) increase in serum iron was associated with increased GrimAge acceleration (GrimAA, Beta IVW = 0.27, P = 8.54E−03 in 2014 datasets; Beta IVW = 0.31, P = 1.25E−02 in 2021 datasets), HannumAge acceleration (HannumAA, Beta IVW = 0.32, P = 4.50E−03 in 2014 datasets; Beta IVW = 0.32, P = 8.03E−03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, Beta IVW = 0.34, P = 5.33E−04 in 2014 datasets; Beta IVW = 0.49, P = 9.94E−04 in 2021 datasets). Similar results were also observed in transferrin saturation. While transferrin manifested a negative association with epigenetic age accelerations (EAAs) sensitivity analyses. Besides, lack of solid evidence to support a causal relationship from EAAs to iron-related biomarkers. Conclusions The results of present investigation unveiled the causality of iron overload on acceleration of epigenetic clocks. Researches are warranted to illuminate the...