DNA methylation aging signatures of multiple metals exposure and their mediation effects in metal-associated mortality : Evidence from the Dongfeng-Tongji cohort study
Copyright © 2023 Elsevier B.V. All rights reserved..
Humans were exposed to multiple metals, but the impact of metals on DNA methylation-age (DNAm-age), a well-recognized aging measure, remains inconclusive. This study included 2942 participants from the Dongfeng-Tongji cohort. We detected their plasma concentrations of 23 metals and determined their genome-wide DNA methylation using the Illumina Human-MethylationEPIC BeadChip. Five DNAm-age acceleration indexes (DAIs), including HannumAge-Accel, HorvathAge-Accel, PhenoAge-Accel, GrimAge-Accel (residual from regressing corresponding DNAm-age on chronological age) and DNAm-mortality score (DNAm-MS), were separately calculated. We found that each 1-unit increase in ln-transformed copper (Cu) was associated with a separate 1.02-, 0.83- and 0.07-unit increase in PhenoAge-Accel, GrimAge-Accel, and DNAm-MS (all FDR<0.05). Each 1-unit increase in ln-transformed nickel (Ni) was associated with a 0.34-year increase in PhenoAge-Accel, while each 1-unit increase in ln-transformed strontium (Sr) was associated with a 0.05-unit increase in DNAm-MS. The Cu, Ni and Sr showed joint positive effects on above three DAIs. PhenoAge-Accel, GrimAge-Accel, and DNAm-MS mediated a separate 6.5%, 12.3%, 6.0% of the positive association between Cu and all-cause mortality; GrimAge-Accel mediated 14.3% of the inverse association of selenium with all-cause mortality. Our findings revealed the effects of Cu, Ni, Sr and their co-exposure on accelerated aging and highlighted mediation roles of DNAm-age on metal-associated mortality.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:465 |
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| Enthalten in: |
Journal of hazardous materials - 465(2024) vom: 05. Feb., Seite 133200 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Chenming [VerfasserIn] |
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| Links: |
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| Themen: |
7OV03QG267 |
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| Anmerkungen: |
Date Completed 08.02.2024 Date Revised 08.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jhazmat.2023.133200 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a Humans were exposed to multiple metals, but the impact of metals on DNA methylation-age (DNAm-age), a well-recognized aging measure, remains inconclusive. This study included 2942 participants from the Dongfeng-Tongji cohort. We detected their plasma concentrations of 23 metals and determined their genome-wide DNA methylation using the Illumina Human-MethylationEPIC BeadChip. Five DNAm-age acceleration indexes (DAIs), including HannumAge-Accel, HorvathAge-Accel, PhenoAge-Accel, GrimAge-Accel (residual from regressing corresponding DNAm-age on chronological age) and DNAm-mortality score (DNAm-MS), were separately calculated. We found that each 1-unit increase in ln-transformed copper (Cu) was associated with a separate 1.02-, 0.83- and 0.07-unit increase in PhenoAge-Accel, GrimAge-Accel, and DNAm-MS (all FDR<0.05). Each 1-unit increase in ln-transformed nickel (Ni) was associated with a 0.34-year increase in PhenoAge-Accel, while each 1-unit increase in ln-transformed strontium (Sr) was associated with a 0.05-unit increase in DNAm-MS. The Cu, Ni and Sr showed joint positive effects on above three DAIs. PhenoAge-Accel, GrimAge-Accel, and DNAm-MS mediated a separate 6.5%, 12.3%, 6.0% of the positive association between Cu and all-cause mortality; GrimAge-Accel mediated 14.3% of the inverse association of selenium with all-cause mortality. Our findings revealed the effects of Cu, Ni, Sr and their co-exposure on accelerated aging and highlighted mediation roles of DNAm-age on metal-associated mortality | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a All-cause mortality | |
| 650 | 4 | |a Biological aging | |
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| 700 | 1 | |a Zhong, Guorong |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chenliang |e verfasserin |4 aut | |
| 700 | 1 | |a Hong, Shiru |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a You, Yingqian |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Tianhao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yuxi |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shengli |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yichi |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chaolong |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Huan |e verfasserin |4 aut | |
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