Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study
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 de...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-10-01
|
| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-023-01575-w |
| _version_ | 1797558866252136448 |
|---|---|
| author | Zhihao Wang Yi Liu Shuxin Zhang Yunbo Yuan Siliang Chen Wenhao Li Mingrong Zuo Yufan Xiang Tengfei Li Wanchun Yang Yuan Yang Yanhui Liu |
| author_facet | Zhihao Wang Yi Liu Shuxin Zhang Yunbo Yuan Siliang Chen Wenhao Li Mingrong Zuo Yufan Xiang Tengfei Li Wanchun Yang Yuan Yang Yanhui Liu |
| author_sort | Zhihao Wang |
| collection | DOAJ |
| description | 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, BetaIVW = 0.27, P = 8.54E−03 in 2014 datasets; BetaIVW = 0.31, P = 1.25E−02 in 2021 datasets), HannumAge acceleration (HannumAA, BetaIVW = 0.32, P = 4.50E−03 in 2014 datasets; BetaIVW = 0.32, P = 8.03E−03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, BetaIVW = 0.34, P = 5.33E−04 in 2014 datasets; BetaIVW = 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 underlying mechanisms and formulate strategies for potential interventions. |
| first_indexed | 2024-03-10T17:37:24Z |
| format | Article |
| id | doaj.art-4cf2327118c246a491ec4542486909f6 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-10T17:37:24Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-4cf2327118c246a491ec4542486909f62023-11-20T09:48:25ZengBMCClinical Epigenetics1868-70832023-10-0115111310.1186/s13148-023-01575-wEffects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization studyZhihao Wang0Yi Liu1Shuxin Zhang2Yunbo Yuan3Siliang Chen4Wenhao Li5Mingrong Zuo6Yufan Xiang7Tengfei Li8Wanchun Yang9Yuan Yang10Yanhui Liu11Department of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Thoracic Surgery and Institute of Thoracic Oncology, West China Hospital, Sichuan UniversityDepartment of Critical Care Medicine, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityAbstract 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, BetaIVW = 0.27, P = 8.54E−03 in 2014 datasets; BetaIVW = 0.31, P = 1.25E−02 in 2021 datasets), HannumAge acceleration (HannumAA, BetaIVW = 0.32, P = 4.50E−03 in 2014 datasets; BetaIVW = 0.32, P = 8.03E−03 in 2021 datasets) and Intrinsic epigenetic age acceleration (IEAA, BetaIVW = 0.34, P = 5.33E−04 in 2014 datasets; BetaIVW = 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 underlying mechanisms and formulate strategies for potential interventions.https://doi.org/10.1186/s13148-023-01575-wIron metabolismIron homeostasisSenescenceAgingEpigenetic age accelerationMendelian randomization |
| spellingShingle | Zhihao Wang Yi Liu Shuxin Zhang Yunbo Yuan Siliang Chen Wenhao Li Mingrong Zuo Yufan Xiang Tengfei Li Wanchun Yang Yuan Yang Yanhui Liu Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study Clinical Epigenetics Iron metabolism Iron homeostasis Senescence Aging Epigenetic age acceleration Mendelian randomization |
| title | Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study |
| title_full | Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study |
| title_fullStr | Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study |
| title_full_unstemmed | Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study |
| title_short | Effects of iron homeostasis on epigenetic age acceleration: a two-sample Mendelian randomization study |
| title_sort | effects of iron homeostasis on epigenetic age acceleration a two sample mendelian randomization study |
| topic | Iron metabolism Iron homeostasis Senescence Aging Epigenetic age acceleration Mendelian randomization |
| url | https://doi.org/10.1186/s13148-023-01575-w |
| work_keys_str_mv | AT zhihaowang effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT yiliu effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT shuxinzhang effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT yunboyuan effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT siliangchen effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT wenhaoli effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT mingrongzuo effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT yufanxiang effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT tengfeili effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT wanchunyang effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT yuanyang effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy AT yanhuiliu effectsofironhomeostasisonepigeneticageaccelerationatwosamplemendelianrandomizationstudy |