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Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      DNA methylation of the\n                      <jats:italic>ELOVL2<\/jats:italic>\n                      (Elongation of Very Long Chain Fatty Acids Protein 2) promoter is one of the most robust molecular biomarkers for chronological age; however, whether\n                      <jats:italic>ELOVL2<\/jats:italic>\n                      plays a functional role in brain aging and immunosenescence, and whether the\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype modulates these effects, has not been fully explored. This study investigated the associations among\n                      <jats:italic>ELOVL<\/jats:italic>\n                      2 methylation,\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype, and neurophysiological changes in the brain, as well as indicators of immunosenescence of peripheral blood T cells during aging.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined 72 non-demented volunteers aged 20\u201388 years, stratified by\n                      <jats:italic>APOE<\/jats:italic>\n                      genotype (41\n                      <jats:italic>APOE<\/jats:italic>\n                      -, 31\n                      <jats:italic>APOE<\/jats:italic>\n                      +).\n                      <jats:italic>ELOVL2<\/jats:italic>\n                      methylation levels were measured via bisulfite conversion and pyrosequencing. Participants underwent cognitive screening, auditory P3 event-related potential (ERP) recordings, and resting-state MRI functional connectivity (rsFC) assessments. In a subgroup of 18 healthy subjects, we examined peripheral blood T-cell subsets and analyzed the association of CD3\n                      <jats:sup>+<\/jats:sup>\n                      HLA-DR\n                      <jats:sup>+<\/jats:sup>\n                      T cells with\n                      <jats:italic>ELOVL2<\/jats:italic>\n                      methylation and neurophysiological characteristics.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>ELOVL<\/jats:italic>\n                      2 CpG promoter methylation (chr 6:11044880. GRCh37) was associated with P3 ERP latency in both the overall sample and\n                      <jats:italic>APOE4<\/jats:italic>\n                      + carriers, remaining significant even after adjusting for age; however, this association was not significant in\n                      <jats:italic>APOE4<\/jats:italic>\n                      - individuals. DNA methylation of\n                      <jats:italic>ELOVL<\/jats:italic>\n                      2 was inversely correlated with fMRI rsFC in the salience-, and memory-related, and central autonomic networks, indicating disrupted connectivity within these networks. An increased proportion of CD3\n                      <jats:sup>+<\/jats:sup>\n                      cells expressing the immune activation marker HLA-DR was correlated with elevated\n                      <jats:italic>ELOVL<\/jats:italic>\n                      2 methylation level and with decreased fMRI rsFC in brain networks, including circuits related to the DMN medial prefrontal cortex, amygdala, and cerebellum.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The results imply a close link between\n                      <jats:italic>ELOVL2<\/jats:italic>\n                      methylation, inflammaging and brain dysfunction, which is modulated by\n                      <jats:italic>APOE4<\/jats:italic>\n                      + genotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803497","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:21:34Z","timestamp":1784002894000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of the methylation of age-related epigenetic marker ELOVL2 with neurophysiological alterations and immunosenescence during aging and its modulation by the APOE genotype"],"prefix":"10.3389","volume":"17","author":[{"given":"Natalya V.","family":"Ponomareva","sequence":"first","affiliation":[{"name":"Russian Center of Neurology and Neurosciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina L.","family":"Kuznetsova","sequence":"additional","affiliation":[{"name":"Vavilov Institute of General Genetics, Russian Academy of Sciences","place":["Moscow, 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