Reduced Accumulation Rate and Morphological Changes of Newly Generated Myelinating Oligodendrocytes in the Corpus Callosum of Aged Mice

ABSTRACT The activity of oligodendrocyte progenitor cells (OPCs) and oligodendrocytes (OLs) throughout life drives myelination, which is crucial for rapid neuronal communication. 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 Pdgfra‐CreER T2 :Tau‐mGFP double transgenic mice to selectively label and visualize newly generated OLs in aged (78‐week‐old) mice and compared them with those in young (8‐week‐old) 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‐related impairments in the differentiation efficiency of aged OPCs and age‐related 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.