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

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

doi:10.17691/stm2021.13.3.03

Abstract

The aim of the study was to conduct a functional analysis of sex-specific age-related changes in DNA methylation.Materials and MethodsThe 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.ResultsThe 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).ConclusionOur studies reveal fundamental features of sex-dependent changes in methylation of CpG sites with variance increasing, which may indicate differences in age-related changes.

Highlights

For many decades, the question of what causes the differences in life expectancy for males and females remains unresolved
We considered a methylation dataset GSE87571 [11] obtained using the Illumina Infinium HumanMethylation450K BeadChip (USA) on blood DNA from the Gene Expression Omnibus (GEO) datasets repository [12]
We identified CpG sites having significant methylation changes with age

Summary

Introduction

The question of what causes the differences in life expectancy for males and females remains unresolved. Longitudinal population studies conducted in different countries and times show that females live longer than males [1]. The difference in life expectancy between males and females varies depending on the region of residence, reaching a maximum of 9 years in Russia. There is an interesting paradox of the low life expectancy of males compared to females and, at the same time, a higher morbidity rate in females, which has not yet found an answer [2]. Recent reports on COVID-19 cases in different countries indicate a sex bias in mortality rates — around 60–70% of the fatal cases were among males [3].

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