Today: Dec 22, 2024
RU / EN
Last update: Oct 30, 2024
Sex-Specific Age-Related Changes in Methylation of Certain Genes

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

Kondakova E.V., Vershinina O.S., Lopatenko M.V., Franceschi C., Ivanchenko M.V., Vedunova M.V.
Key words: DNA methylation; CpG sites; age-associated diseases; sex-specific changes.
2021, volume 13, issue 3, page 26.

Full text

html pdf
1417
1161

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.

  1. Luy M., Gast K. Do women live longer or do men die earlier? Reflections on the causes of sex differences in life expectancy. Gerontology 2014; 60(2): 143–153, https://doi.org/10.1159/000355310.
  2. Oksuzyan A., Shkolnikova M., Vaupel J.W., Christensen K., Shkolnikov V.M. Sex differences in health and mortality in Moscow and Denmark. Eur J Epidemiol 2014; 29(4): 243–252, https://doi.org/10.1007/s10654-014-9893-4.
  3. Spagnolo P.A., Manson J.E., Joffe H. Sex and gender differences in health: what the COVID-19 pandemic can teach us. Ann Intern Med 2020; 173(5): 385–386, https://doi.org/10.7326/m20-1941.
  4. Mendy V.L., Rowell-Cunsolo T., Bellerose M., Vargas R., Zhang L., Enkhmaa B. Temporal trends in hypertension death rate in Mississippi, 2000–2018. Am J Hypertens 2021; hpab068, https://doi.org/10.1093/ajh/hpab068.
  5. Cai A., Zhou D., Liu L., Zhou Y., Tang S., Feng Y. Age-related alterations in cardiac and arterial structure and function in hypertensive women and men. J Clin Hypertens (Greenwich) 2021, https://doi.org/10.1111/jch.14262.
  6. Haupt S., Caramia F., Klein S.L., Rubin J.B., Haupt Y. Sex disparities matter in cancer development and therapy. Nat Rev Cancer 2021, https://doi.org/10.1038/s41568-021-00348-y.
  7. Austad S.N. Why women live longer than men: sex differences in longevity. Gend Med 2006; 3(2): 79–92, https://doi.org/10.1016/s1550-8579(06)80198-1.
  8. Jung M., Pfeifer G. Aging and DNA methylation. BMC Biol 2015; 13: 7, https://doi.org/10.1186/s12915-015-0118-4.
  9. Horvath S., Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet 2018; 19(6): 371–384, https://doi.org/10.1038/s41576-018-0004-3.
  10. Field A.E., Robertson N.A., Wang T., Havas A., Ideker T., Adams P.D. DNA methylation clocks in aging: categories, causes, and consequences. Mol Cell 2018; 71(6): 882–895, https://doi.org/10.1016/j.molcel.2018.08.008.
  11. Johansson A., Enroth S., Gyllensten U. Continuous aging of the human DNA methylome throughout the human lifespan. PloS One 2013; 8(6): e67378, https://doi.org/10.1371/journal.pone.0067378.
  12. Barrett T., Troup D.B., Wilhite S.E., Ledoux P., Rudnev D., Evangelista C., Kim I.F., Soboleva A., Tomashevsky M., Marshall K.A., Phillippy K.H., Sherman P.M., Muertter R.N., Edgar R. NCBI GEO: archive for high-throughput functional genomic data. Nucleic Acids Res 2009; 37: D885–D890, https://doi.org/10.1093/nar/gkn764.
  13. Inoshita M., Numata S., Tajima A., Kinoshita M., Umehara H., Yamamori H., Hashimoto R., Imoto I., Ohmori T. Sex differences of leukocytes DNA methylation adjusted for estimated cellular proportions. Biol Sex Differ 2015; 6: 11, https://doi.org/10.1186/s13293-015-0029-7.
  14. Singmann P., Shem-Tov D., Wahl S., Grallert H., Fiorito G., Shin S.Y., Schramm K., Wolf P., Kunze S., Baran Y., Guarrera S., Vineis P., Krogh V., Panico S., Tumino R., Kretschmer A., Gieger C., Peters A., Prokisch H., Relton C.L., Matullo G., Illig T., Waldenberger M., Halperin E. Characterization of whole-genome autosomal differences of DNA methylation between men and women. Epigenetics Chromatin 2015; 8: 43, https://doi.org/10.1186/s13072-015-0035-3.
  15. Pellegrini C., Pirazzini C., Sala C., Sambati L., Yusipov I., Kalyakulina A., Ravaioli F., Kwiatkowska K.M., Durso D.F., Ivanchenko M., Monti D., Lodi R., Franceschi C., Cortelli P., Garagnani P., Bacalini M.G. A meta-analysis of brain DNA methylation across sex, age, and Alzheimer’s disease points for accelerated epigenetic aging in neurodegeneration. Front Aging Neurosci 2021; 13: 639428, https://doi.org/10.3389/fnagi.2021.639428.
  16. Mi H., Muruganujan A., Thomas P.D. PANTHER in 2013: modeling the evolution of gene function, and other gene attributes, in the context of phylogenetic trees. Nucleic Acids Research 2013; 41: D377–D386, https://doi.org/10.1093/nar/gks1118.
  17. Ren X., Kuan P.F. MethylGSA: a Bioconductor package and Shiny app for DNA methylation data length bias adjustment in gene set testing. Bioinformatics 2019; 35(11): 1958–1959, https://doi.org/10.1093/bioinformatics/bty892.
  18. Ritchie M.E., Phipson B., Wu D., Hu Y., Law C.W., Shi W., Smyth G.K. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research 2015; 43(7): e47, https://doi.org/10.1093/nar/gkv007.
  19. Jiao X., Sherman B.T., Huang da W., Stephens R., Baseler M.W., Lane H.C., Lempicki R.A. DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics 2012; 28(13): 1805–1806, https://doi.org/10.1093/bioinformatics/bts251.
  20. Horvath S. DNA methylation age of human tissues and cell types. Genome Biol 2013; 14(10): R115, https://doi.org/10.1186/gb-2013-14-10-r115.
  21. DNA Methylation Age Calculator. URL: https://dnamage.genetics.ucla.edu/home.
  22. Jones P.A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13(7): 484–492, https://doi.org/10.1038/nrg3230.
  23. Xiao F.H., Wang H.T., Kong Q.P. Dynamic DNA methylation during aging: a “prophet” of age-related outcomes. Front Genet 2019; 10: 107, https://doi.org/10.3389/fgene.2019.00107.
  24. Vershinina O., Bacalini M.G., Zaikin A., Franceschi C., Ivanchenko M. Disentangling age-dependent DNA methylation: deterministic, stochastic, and nonlinear. Sci Rep 2021; 11(1): 9201, https://doi.org/10.1038/s41598-021-88504-0.
  25. Yusipov I.I., Bacalini M.G., Kalyakulina A.I., Krivonosov M., Pirazzini C., Gensous N., Ravaioli F., Milazzo M., Giuliani C., Vedunova M., Fiorito G., Gagliardi A., Polidoro S., Garagnani P., Ivanchenko M., Franceschi C. Age-related DNA methylation changes are sex-specific: a comprehensive assessment. Aging (Albany NY) 2020; 23(12): 24057–24080, https://doi.org/10.18632/aging.202251.
  26. Austad S.N., Bartke A. Sex differences in longevity and in responses to anti-aging interventions: a mini-review. Gerontology 2015; 62(1): 40–46, https://doi.org/10.1159/000381472.
  27. Palmisano B.T., Zhu L., Eckel R.H., Stafford J.M. Sex differences in lipid and lipoprotein metabolism. Mol Metab 2018; 15: 45–55, https://doi.org/10.1016/j.molmet.2018.05.008.
  28. Giacometti L.L., Barker J.M. Sex differences in the glutamate system: implications for addiction. Neurosci Biobehav Rev 2020; 113: 157–168, https://doi.org/10.1016/j.neubiorev.2020.03.010.
  29. Hodes G.E., Epperson C.N. Sex differences in vulnerability and resilience to stress across the life span. Biol Psychiatry 2019; 86(6): 421–432, https://doi.org/10.1016/j.biopsych.2019.04.028.
Kondakova E.V., Vershinina O.S., Lopatenko M.V., Franceschi C., Ivanchenko M.V., Vedunova M.V. Sex-Specific Age-Related Changes in Methylation of Certain Genes. Sovremennye tehnologii v medicine 2021; 13(3): 26, https://doi.org/10.17691/stm2021.13.3.03


Journal in Databases

pubmed_logo.jpg

web_of_science.jpg

scopus.jpg

crossref.jpg

ebsco.jpg

embase.jpg

ulrich.jpg

cyberleninka.jpg

e-library.jpg

lan.jpg

ajd.jpg

SCImago Journal & Country Rank