Sex-Specific Age-Related Changes in Methylation of Certain Genes

E V Kondakova; O S Vershinina; M V Lopatenko; C Franceschi; M V Ivanchenko; M V Vedunova

doi:10.17691/stm2021.13.3.03

Sex-Specific Age-Related Changes in Methylation of Certain Genes

Sovrem Tekhnologii Med. 2021;13(3):26-31. doi: 10.17691/stm2021.13.3.03. Epub 2021 Jun 28.

Authors

E V Kondakova¹, O S Vershinina², M V Lopatenko³, C Franceschi⁴, M V Ivanchenko⁵, M V Vedunova⁶

Affiliations

¹ Assistant, Department of General and Medical Genetics, Institute of Biology and Biomedicine; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.
² Junior Researcher, Department of Applied Mathematics, Institute of Information Technologies, Mathematics and Mechanics; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.
³ Student, Institute of Biology and Biomedicine; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.
⁴ Professor Emeritus, Senior Researcher, Photonics Center, Department of Fundamental and Applied Research; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia; Mater Studiorum; University of Bologna, 33 Via Zamboni, Bologna, 40126, Italy.
⁵ Head of the Department of Applied Mathematics, Institute of Information Technologies, Mathematics and Mechanics; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.
⁶ Head of the Department of General and Medical Genetics, Institute of Biology and Biomedicine; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia; Director of the Institute of Biology and Biomedicine; National Research Lobachevsky State University of Nizhni Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia.

Abstract

The aim of the study was to conduct a functional analysis of sex-specific age-related changes in DNA methylation.

Materials and methods: The study used a GSE87571 methylation dataset obtained from the blood DNA of 729 individuals aged 14 to 94 using the Illumina Infinium HumanMethylation450K BeadChip (USA). Gene ontology analysis was performed for 3 groups of genes (females, males, and duplicates) using the PANTHER database. The DAVID platform was used to perform KEGG metabolic pathway analysis.

Results: The studies revealed unique for males and females changes in methylation of CpG sites, associated with certain metabolic processes. It was demonstrated that most of the CpG sites, for which methylation changes with age were revealed in both sexes, are associated with the genes responsible for the development and functioning of the nervous system. In males, unique age-related methylation changes affect CpG sites associated with changes in the immune system and lipid metabolism. In females, most CpGs are associated with changes involved in transcription and translation processes. Analysis of biological functions by KEGG revealed that a unique process associated with age-related changes in methylation of the glutamatergic system is typical for males. In females, unique biological processes with age-related changes include genes responsible for the development of diabetes and genes associated with cAMP signaling cascades (KEGG:04024).

Conclusion: Our studies reveal fundamental features of sex-dependent changes in methylation of CpG sites with variance increasing, which may indicate differences in age-related changes.

Keywords: CpG sites; DNA methylation; age-associated diseases; sex-specific changes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
CpG Islands / genetics
DNA Methylation* / genetics
Female
Humans
Male
Middle Aged
Young Adult

Grants and funding

Research funding. This study was supported by the Ministry of Science and Higher Education of the Russian Federation (project No.0729-2020-0061).