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OLs in the aging brain demonstrate a reduced capacity for myelin formation and maintenance, but the underlying differentiation of individual OLs and morphological changes of their myelin in aging remain unclear. Here, we utilized <jats:italic>Pdgfra\u2010CreER<\/jats:italic>\n<jats:sup>\n<jats:italic>T2<\/jats:italic>\n<\/jats:sup>:<jats:italic>Tau\u2010mGFP<\/jats:italic> double transgenic mice to selectively label and visualize newly generated OLs in aged (78\u2010week\u2010old) mice and compared them with those in young (8\u2010week\u2010old) mice. We revealed a significantly lower percentage of newly generated OLs that differentiated into mature OLs and a decreased rate of myelinating OLs accumulation in aged mice compared with young mice. Additionally, newly generated myelinating mature OLs in aged mice demonstrated significantly greater height compared with those in young mice. Furthermore, myelin internodes were significantly shorter and significantly fewer in aged mice compared with young mice. Our results indicate age\u2010related impairments in the differentiation efficiency of aged OPCs and age\u2010related morphological changes in OLs. These alterations in newly generated OLs may contribute to impaired myelination, reduced myelin turnover, and disrupted myelin maintenance in aged mice.<\/jats:p>","DOI":"10.1002\/glia.70070","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T11:30:26Z","timestamp":1754047826000},"page":"2322-2334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Reduced Accumulation Rate and Morphological Changes of Newly Generated Myelinating Oligodendrocytes in the Corpus Callosum of Aged Mice"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5361-4844","authenticated-orcid":false,"given":"Sasikarn","family":"Looprasertkul","sequence":"first","affiliation":[{"name":"Department of Anatomy, Division of Histology and Cell Biology, School of Medicine Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8052-6624","authenticated-orcid":false,"given":"Reiji","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Histology and Cell Biology, School of Medicine Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-7546","authenticated-orcid":false,"given":"Yasuyuki","family":"Osanai","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Histology and Cell Biology, School of Medicine Jichi Medical University  Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6536-2753","authenticated-orcid":false,"given":"Nobuhiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Histology and Cell Biology, School of Medicine Jichi Medical University  Shimotsuke Japan"},{"name":"Division of Ultrastructural Research National Institute for Physiological Sciences  Okazaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010021\u201001105\u20107"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201051016\u20102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2015.01.016"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22379"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896\u20106273(01)00296\u20103"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.40.8.769"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4183"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.134645"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.RA120.002102"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010022\u201000621\u20104"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropsychologia.2023.108533"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1253851"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhs379"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9073"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410010607"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/164490a0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100120\u20106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030159"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.90964.3"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09603"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108413"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474\u20109726.2009.00462.x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2024.111959"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2147\/jir.S338242"},{"key":"e_1_2_10_26_1","first-page":"69","volume-title":"Methods in Cell Biology","author":"Mathews E. 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