ArticleAging cell2023
Protein phosphatase 2A activators reverse age-related behavioral changes by targeting neural cell senescence.
Article in Aging cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- PP2A Activation as a Senotherapeutic in Neuroblastoma.Cancers · 2026Article
- PPP2R2C confers radioresistance in nasopharyngeal carcinoma by suppressing ferroptosis via RPS27L stabilization.Cell death & disease · 2026Article
- The Use of Nutritional Interventions to Enhance Genomic Stability in Mice and Delay Aging.Nutrients · 2026Review
- Mitochondrial stress orchestrates chromatin remodeling and longevity via phosphoregulation of the NuRD component LIN-40.Science China. Life sciences · 2025Article
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- Senotherapeutic repurposing of metformin for age-related diseases and their signaling pathways.Molecular biology reports · 2025Review
- Article
- Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.Aging and disease · 2024Review
- Heat shock response during the resolution of inflammation and its progressive suppression in chronic-degenerative inflammatory diseases.Cell stress & chaperones · 2024Review
- Challenges in anti-aging medicine-trends in biomarker discovery and therapeutic interventions for a healthy lifespan.Journal of cellular and molecular medicine · 2023Review
- Protein phosphatase 2A activators reverse age-related behavioral changes by targeting neural cell senescence.Aging cell · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The contribution of cellular senescence to the behavioral changes observed in the elderly remains elusive. Here, we observed that aging is associated with a decline in protein phosphatase 2A (PP2A) activity in the brains of zebrafish and mice. Moreover, drugs activating PP2A reversed age-related behavioral changes. We developed a transgenic zebrafish model to decrease PP2A activity in the brain through knockout of the ppp2r2c gene encoding a regulatory subunit of PP2A. Mutant fish exhibited the behavioral phenotype observed in old animals and premature accumulation of neural cells positive for markers of cellular senescence, including senescence-associated β-galactosidase, elevated levels cdkn2a/b, cdkn1a, senescence-associated secretory phenotype gene expression, and an increased level of DNA damage signaling. The behavioral and cell senescence phenotypes were reversed in mutant fish through treatment with the senolytic ABT263 or diverse PP2A activators as well as through cdkn1a or tp53 gene ablation. Senomorphic function of PP2A activators was demonstrated in mouse primary neural cells with downregulated Ppp2r2c. We conclude that PP2A reduction leads to neural cell senescence thereby contributing to age-related behavioral changes and that PP2A activators have senotherapeutic properties against deleterious behavioral effects of brain aging.
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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.