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Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes
Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157596/ https://www.ncbi.nlm.nih.gov/pubmed/35664466 http://dx.doi.org/10.3389/fpsyt.2022.870656 |
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author | Pérez-Aldana, Blanca Estela Martínez-Magaña, José Jaime Mayén-Lobo, Yerye Gibrán Dávila-Ortiz de Montellano, David José Aviña-Cervantes, Carlos Luis Ortega-Vázquez, Alberto Genis-Mendoza, Alma Delia Sarmiento, Emmanuel Soto-Reyes, Ernesto Juárez-Rojop, Isela Esther Tovilla-Zarate, Carlos Alfonso González-Castro, Thelma Beatriz Nicolini, Humberto López-López, Marisol Monroy-Jaramillo, Nancy |
author_facet | Pérez-Aldana, Blanca Estela Martínez-Magaña, José Jaime Mayén-Lobo, Yerye Gibrán Dávila-Ortiz de Montellano, David José Aviña-Cervantes, Carlos Luis Ortega-Vázquez, Alberto Genis-Mendoza, Alma Delia Sarmiento, Emmanuel Soto-Reyes, Ernesto Juárez-Rojop, Isela Esther Tovilla-Zarate, Carlos Alfonso González-Castro, Thelma Beatriz Nicolini, Humberto López-López, Marisol Monroy-Jaramillo, Nancy |
author_sort | Pérez-Aldana, Blanca Estela |
collection | PubMed |
description | Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein–protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes. |
format | Online Article Text |
id | pubmed-9157596 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91575962022-06-02 Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes Pérez-Aldana, Blanca Estela Martínez-Magaña, José Jaime Mayén-Lobo, Yerye Gibrán Dávila-Ortiz de Montellano, David José Aviña-Cervantes, Carlos Luis Ortega-Vázquez, Alberto Genis-Mendoza, Alma Delia Sarmiento, Emmanuel Soto-Reyes, Ernesto Juárez-Rojop, Isela Esther Tovilla-Zarate, Carlos Alfonso González-Castro, Thelma Beatriz Nicolini, Humberto López-López, Marisol Monroy-Jaramillo, Nancy Front Psychiatry Psychiatry Long-term studies have shown significantly lower mortality rates in patients with continuous clozapine (CLZ) treatment than other antipsychotics. We aimed to evaluate epigenetic age and DNA methylome differences between CLZ-treated patients and those without psychopharmacological treatment. The DNA methylome was analyzed using the Infinium MethylationEPIC BeadChip in 31 CLZ-treated patients with psychotic disorders and 56 patients with psychiatric disorders naive to psychopharmacological treatment. Delta age (Δage) was calculated as the difference between predicted epigenetic age and chronological age. CLZ-treated patients were stratified by sex, age, and years of treatment. Differential methylation sites between both groups were determined using linear regression models. The Δage in CLZ-treated patients was on average lower compared with drug-naive patients for the three clocks analyzed; however, after data-stratification, this difference remained only in male patients. Additional differences were observed in Hannum and Horvath clocks when comparing chronological age and years of CLZ treatment. We identified 44,716 differentially methylated sites, of which 87.7% were hypomethylated in CLZ-treated patients, and enriched in the longevity pathway genes. Moreover, by protein–protein interaction, AMPK and insulin signaling pathways were found enriched. CLZ could promote a lower Δage in individuals with long-term treatment and modify the DNA methylome of the longevity-regulating pathways genes. Frontiers Media S.A. 2022-05-18 /pmc/articles/PMC9157596/ /pubmed/35664466 http://dx.doi.org/10.3389/fpsyt.2022.870656 Text en Copyright © 2022 Pérez-Aldana, Martínez-Magaña, Mayén-Lobo, Dávila-Ortiz de Montellano, Aviña-Cervantes, Ortega-Vázquez, Genis-Mendoza, Sarmiento, Soto-Reyes, Juárez-Rojop, Tovilla-Zarate, González-Castro, Nicolini, López-López and Monroy-Jaramillo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Pérez-Aldana, Blanca Estela Martínez-Magaña, José Jaime Mayén-Lobo, Yerye Gibrán Dávila-Ortiz de Montellano, David José Aviña-Cervantes, Carlos Luis Ortega-Vázquez, Alberto Genis-Mendoza, Alma Delia Sarmiento, Emmanuel Soto-Reyes, Ernesto Juárez-Rojop, Isela Esther Tovilla-Zarate, Carlos Alfonso González-Castro, Thelma Beatriz Nicolini, Humberto López-López, Marisol Monroy-Jaramillo, Nancy Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title | Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title_full | Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title_fullStr | Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title_full_unstemmed | Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title_short | Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes |
title_sort | clozapine long-term treatment might reduce epigenetic age through hypomethylation of longevity regulatory pathways genes |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157596/ https://www.ncbi.nlm.nih.gov/pubmed/35664466 http://dx.doi.org/10.3389/fpsyt.2022.870656 |
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