Clozapine Long-Term Treatment Might Reduce Epigenetic Age Through Hypomethylation of Longevity Regulatory Pathways Genes.
DNA methylome
clozapine
epigenetic age
longevity
psychotic disorders
Journal
Frontiers in psychiatry
ISSN: 1664-0640
Titre abrégé: Front Psychiatry
Pays: Switzerland
ID NLM: 101545006
Informations de publication
Date de publication:
2022
2022
Historique:
received:
07
02
2022
accepted:
29
03
2022
entrez:
6
6
2022
pubmed:
7
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35664466
doi: 10.3389/fpsyt.2022.870656
pmc: PMC9157596
doi:
Types de publication
Journal Article
Langues
eng
Pagination
870656Informations de copyright
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.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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