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Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters
Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corre...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634256/ https://www.ncbi.nlm.nih.gov/pubmed/37953967 http://dx.doi.org/10.1177/25168657231206301 |
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author | Jung, Alesia M Furlong, Melissa A Goodrich, Jaclyn M Cardenas, Andres Beitel, Shawn C Littau, Sally R Caban-Martinez, Alberto J Gulotta, John J Wallentine, Darin D Urwin, Derek Gabriel, Jamie Hughes, Jeffrey Graber, Judith M Grant, Casey Burgess, Jefferey L |
author_facet | Jung, Alesia M Furlong, Melissa A Goodrich, Jaclyn M Cardenas, Andres Beitel, Shawn C Littau, Sally R Caban-Martinez, Alberto J Gulotta, John J Wallentine, Darin D Urwin, Derek Gabriel, Jamie Hughes, Jeffrey Graber, Judith M Grant, Casey Burgess, Jefferey L |
author_sort | Jung, Alesia M |
collection | PubMed |
description | Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases. |
format | Online Article Text |
id | pubmed-10634256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-106342562023-11-10 Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters Jung, Alesia M Furlong, Melissa A Goodrich, Jaclyn M Cardenas, Andres Beitel, Shawn C Littau, Sally R Caban-Martinez, Alberto J Gulotta, John J Wallentine, Darin D Urwin, Derek Gabriel, Jamie Hughes, Jeffrey Graber, Judith M Grant, Casey Burgess, Jefferey L Epigenet Insights Original Research Epigenetic changes may be biomarkers of health. Epigenetic age acceleration (EAA), the discrepancy between epigenetic age measured via epigenetic clocks and chronological age, is associated with morbidity and mortality. However, the intersection of epigenetic clocks with microRNAs (miRNAs) and corresponding miRNA-based health implications have not been evaluated. We analyzed DNA methylation and miRNA profiles from blood sampled among 332 individuals enrolled across 2 U.S.-based firefighter occupational studies (2015-2018 and 2018-2020). We considered 7 measures of EAA in leukocytes (PhenoAge, GrimAge, Horvath, skin-blood, and Hannum epigenetic clocks, and extrinsic and intrinsic epigenetic age acceleration). We identified miRNAs associated with EAA using individual linear regression models, adjusted for sex, race/ethnicity, chronological age, and cell type estimates, and investigated downstream effects of associated miRNAs with miRNA enrichment analyses and genomic annotations. On average, participants were 38 years old, 88% male, and 75% non-Hispanic white. We identified 183 of 798 miRNAs associated with EAA (FDR q < 0.05); 126 with PhenoAge, 59 with GrimAge, 1 with Horvath, and 1 with the skin-blood clock. Among miRNAs associated with Horvath and GrimAge, there were 61 significantly enriched disease annotations including age-related metabolic and cardiovascular conditions and several cancers. Enriched pathways included those related to proteins and protein modification. We identified miRNAs associated with EAA of multiple epigenetic clocks. PhenoAge had more associations with individual miRNAs, but GrimAge and Horvath had greater implications for miRNA-associated pathways. Understanding the relationship between these epigenetic markers could contribute to our understanding of the molecular underpinnings of aging and aging-related diseases. SAGE Publications 2023-11-08 /pmc/articles/PMC10634256/ /pubmed/37953967 http://dx.doi.org/10.1177/25168657231206301 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Research Jung, Alesia M Furlong, Melissa A Goodrich, Jaclyn M Cardenas, Andres Beitel, Shawn C Littau, Sally R Caban-Martinez, Alberto J Gulotta, John J Wallentine, Darin D Urwin, Derek Gabriel, Jamie Hughes, Jeffrey Graber, Judith M Grant, Casey Burgess, Jefferey L Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title | Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title_full | Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title_fullStr | Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title_full_unstemmed | Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title_short | Associations Between Epigenetic Age Acceleration and microRNA Expression Among U.S. Firefighters |
title_sort | associations between epigenetic age acceleration and microrna expression among u.s. firefighters |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634256/ https://www.ncbi.nlm.nih.gov/pubmed/37953967 http://dx.doi.org/10.1177/25168657231206301 |
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