{"doi":"10.3390/epigenomes9040038","title":"Tripartite Interaction of Epigenetic Regulation, Brain Aging, and Neuroinflammation: Mechanistic Insights and Therapeutic Implications","abstract":"<jats:p>Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms—such as DNA methylation and histone modification—in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability.</jats:p>","journal":"Epigenomes","year":2025,"id":628661,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1243170,"name":"Hideyuki Nakashima","orcid":"0000-0001-9430-5363","position":1,"is_corresponding":false},{"id":1243172,"name":"Kinichi Nakashima","orcid":"0000-0001-5901-9628","position":2,"is_corresponding":false},{"id":1627747,"name":"Shenghui Mi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Tripartite Interaction of Epigenetic Regulation, Brain Aging, and Neuroinflammation: Mechanistic Insights and Therapeutic Implications","abstract":"<jats:p>Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms—such as DNA methylation and histone modification—in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability.</jats:p>","is_dataset_classified":null,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41133713","pmcid":"PMC12551057","openalex_id":"https://openalex.org/W4414853760","authors":[],"funders":[{"funder_name":"JSPS","grant_id":"JP23H00391","title":null},{"funder_name":"JSPS","grant_id":"JP25H01319","title":null},{"funder_name":"AMED","grant_id":"JP20gm1310008","title":null},{"funder_name":"AMED","grant_id":"JP24wm0625306","title":null},{"funder_name":"JSPS","grant_id":"JP25H01866","title":null},{"funder_name":"AMED","grant_id":"JP23ek0109640","title":null}],"total_grants":6,"fwci":1.7034,"citation_percentile":0.85670539,"influential_citations":0,"citation_trend":[{"year":2026,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2075-4655/9/4/38/pdf?version=1759660207","host_type":"journal"},{"url":"https://www.mdpi.com/2075-4655/9/4/38/pdf?version=1759660207","host_type":"publisher"},{"url":"https://www.mdpi.com/2075-4655/9/4/38/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/epigenomes9040038","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41133713","host_type":"repository"},{"url":"https://doaj.org/article/dde9ae00d4334c35a8d60714d3b1356c","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12551057","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12551057","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12551057?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Neuroinflammation and Neurodegeneration Mechanisms","Tryptophan and brain disorders","Neurogenesis and neuroplasticity mechanisms"],"mesh_terms":[],"keywords":["Epigenetics","Histone","DNA methylation","Neuroinflammation","Epigenetic regulation of neurogenesis","Epigenesis","Disease","Gene expression","Regulation of gene expression","Neurodegenerative disease","brain aging","DNA sensor","Endogenous Dna Ligands"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-05T14:30:36.134571Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}