{"id":"doi:10.1111/acel.70776","kind":"article","title":"In Vivo Partial Cell Reprogramming With Yamanaka Factors Reduced Ischemic Brain Damage in Aging Mice","authors":["Mallavibarrena PR","Martín-López G","Rodríguez-Morales J","Ávila J","Hernández F","Pérez-Álvarez MJ"],"author_count":6,"year":2026,"published":"2026-11-01","venue":"Aging cell","cited_by":0,"doi":"10.1111/acel.70776","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1111/acel.70776","archive_url":"https://space-kitty.com/papers/doi:10.1111/acel.70776","updated":null,"pmid":"42924487","pmcid":"PMC13692703","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13692703/pdf","abstract":"Aging is associated with functional decline and reduced regenerative capacity in the brain, is also the strongest risk factor for ischemic stroke, which remains a leading cause of mortality and long-term disability worldwide, and is associated with impaired functional recovery. Here, we investigated whether short-term partial cellular reprogramming through cyclic expression of Yamanaka factors (OSKM) in a Tet-ON mouse model under Rosa-26 promoter has any impact on ischemic damage in aged mice. To assess ischemic resilience, mice underwent permanent middle cerebral artery occlusion (pMCAo). Forty-eight hours after ischemia, OSKM-induced mice displayed significantly smaller damaged area compared with wild-type controls, accompanied by improved neurological scores and enhanced performance in the tightrope test, suggesting preserved sensorimotor abilities. Notably, myelin integrity was preserved in OSKM-treated mice, as shown by Black-Gold staining and stable MAG and MBP expression, whereas wild-type mice exhibited pronounced demyelination. Given the role of oligodendrocytes in myelin maintenance, we quantified the abundance of their different populations. OSKM induction significantly increased total oligodendrocytes (Olig2 + ) and oligodendrocyte precursor cells (PDGFRα + ) following ischemia, suggesting an enhanced reparative response. Moreover, partial reprogramming preserved neuronal density in the ischemic cortex and prevented the marked astrocytic activation observed in wild-type mice, while microglial responses remained comparable across genotypes. These findings demonstrate that cyclic partial reprogramming in aged mice reduces ischemic damage, highlighting OSKM induction as a promising strategy for enhancing brain resilience during cerebrovascular accidents.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"In Vivo Partial Cell Reprogramming With Yamanaka Factors Reduced Ischemic Brain Damage in Aging Mice\" by Mallavibarrena PR, Martín-López G, Rodríguez-Morales J et al., https://doi.org/10.1111/acel.70776, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}