Association of cytomegalovirus serostatus with ELOVL2 methylation: Implications for lipid metabolism, inflammation, DNA damage, and repair capacity in the MARK-AGE study population
Giacconi, Robertina; Pirazzini, Chiara; Bacalini, Maria Giulia; Garagnani, Paolo; Capri, Miriam; Franceschi, Claudio; Fortunato, Carlo; Pazmay, Gretta Veronica Badillo; Bürkle, Alexander; Villanueva, María Moreno; Cardelli, Maurizio; Piacenza, Francesco; Cecati, Monia; Cianfruglia, Laura; Dollé, Martijn ET; Jansen, Eugène; Grune, Tilman; Gonos, Efstathios S; Weinberger, Birgit; Sikora, Ewa; Zampieri, Michele; Caiafa, Paola; Ciccarone, Fabio; Reale, Anna; Debacq-Chainiaux, Florence; Stuetz, Wolfgang; Hurme, Mikko; Slagboom, P Eline; Bernhardt, Jürgen; Olivieri, Fabiola; Malavolta, Marco
Series / Report no.
Open Access
Type
Journal Article
Article
Article
Language
en
Date
2025-02-28
Research Projects
Organizational Units
Journal Issue
Title
Association of cytomegalovirus serostatus with ELOVL2 methylation: Implications for lipid metabolism, inflammation, DNA damage, and repair capacity in the MARK-AGE study population
Translated Title
Published in
Mech Ageing Dev 2025; 225:112043
Abstract
Cytomegalovirus (CMV) infection has been linked to accelerated biological aging, potentially increasing the risk of cardiovascular disease. DNA methylation of the gene Elongation Of Very Long Chain Fatty Acids-Like 2 (ELOVL2) is a molecular biomarker for aging, and its gene product is involved in polyunsaturated fatty acid synthesis, which impacts immune and inflammatory responses. This study, conducted in the MARK-AGE population, aimed to investigate the relationship between CMV infection and ELOVL2 methylation in adults aged 35-75, as well as the influence of CMV IgG levels on lipid metabolism, inflammation, DNA damage, and DNA repair. Our data revealed a higher prevalence of ischemic heart disease, atrial fibrillation, hypertension, and diabetes in CMV-positive individuals. CMV IgG levels were positively associated with ELOVL2 methylation at specific CpG sites and with increased expression of DNA methyltransferase-1 (DNMT1). CMV IgG was linked to lipid imbalances, such as increased BMI, VLDL-cholesterol, triglycerides, and HDL1-cholesterol. Additionally, ELOVL2 methylation was associated with systemic inflammation markers, lipid parameters and altered T-cell subsets. A negative correlation was observed between CMV IgG levels and both baseline DNA integrity and repair capacity. These results suggest that CMV infection might promote cardiovascular disease through ELOVL2 hypermethylation, lipid dysregulation, inflammation, and DNA damage.