# In Vivo Partial Cell Reprogramming With Yamanaka Factors Reduced Ischemic Brain Damage in Aging Mice

Article · Mallavibarrena PR, Martín-López G, Rodríguez-Morales J, Ávila J, Hernández F, Pérez-Álvarez MJ

- Archive id: doi:10.1111/acel.70776
- Published: 2026-11-01
- Venue: Aging cell
- DOI: https://doi.org/10.1111/acel.70776
- PMID: 42924487
- PMCID: PMC13692703
- Citations: 0
- Source URL: https://doi.org/10.1111/acel.70776
- PDF: https://europepmc.org/articles/PMC13692703/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.