ArticleGeroScience2025
Cognitive rejuvenation in old rats by hippocampal OSKM gene therapy.
Article in GeroScience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Conserved Partial Reprogramming Effects on the Methylome.Epigenomes · 2026Article
- Review
- Targeted neuronal reprogramming rescues memory and neural synchrony in Alzheimer's disease.Molecular biomedicine · 2026Article
- Epigenetic aging and rejuvenation of the brain: drivers, consequences, and interventions.BMB reports · 2026Review
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Article
- From Bench to Bedside: Translating Cellular Rejuvenation Therapies into Clinical Applications.Cells · 2024Review
- Changes in skeletal muscle function during chemotherapy and related factors in patients with acute leukemia.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Article
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Authors and funding
16 authors.
Funding
Abstract
Several studies have indicated that interrupted epigenetic reprogramming using Yamanaka transcription factors (OSKM) can rejuvenate cells from old laboratory animals and humans. However, the potential of OSKM-induced rejuvenation in brain tissue has been less explored. Here, we aimed to restore cognitive performance in 25.3-month-old female Sprague-Dawley rats using OSKM gene therapy for 39 days. Their progress was then compared with the cognitive performance of untreated 3.5-month-old rats as well as old control rats treated with a placebo adenovector. The Barnes maze test, used to assess cognitive performance, demonstrated enhanced cognitive abilities in old rats treated with OSKM compared to old control animals. In the treated old rats, there was a noticeable trend towards improved spatial memory relative to the old controls. Further, OSKM gene expression did not lead to any pathological alterations within the 39 days. Analysis of DNA methylation following OSKM treatment yielded three insights. First, epigenetic clocks for rats suggested a marginally significant epigenetic rejuvenation. Second, chromatin state analysis revealed that OSKM treatment rejuvenated the methylome of the hippocampus. Third, an epigenome-wide association analysis indicated that OSKM expression in the hippocampus of old rats partially reversed the age-related increase in methylation. In summary, the administration of Yamanaka genes via viral vectors rejuvenates the functional capabilities and the epigenetic landscape of the rat hippocampus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.