ArticleAging cell2015
Increased gene dosage of Ink4/Arf and p53 delays age-associated central nervous system functional decline.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Lipidomic profiling reveals age-dependent changes in plasma membrane lipids that affect neural stem cell aging.Science advances · 2026Article
- Induction of chronic asthma up regulated the transcription of senile factors in male rats.BMC molecular and cell biology · 2024Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- An Unanticipated Modulation of Cyclin-Dependent Kinase Inhibitors: The Role of Long Non-Coding RNAs.Cells · 2022Review
- An interdependent network of functional enhancers regulates transcription and EZH2 loading at the INK4a/ARF locus.Cell reports · 2021Article
- Non-Canonical Functions of the ARF Tumor Suppressor in Development and Tumorigenesis.Biomolecules · 2021Review
- How can aging be reversed? Exploring rejuvenation from a damage-based perspective.Advanced genetics (Hoboken, N.J.) · 2020Article
- Aging and Rejuvenation of Neural Stem Cells and Their Niches.Cell stem cell · 2020Review
- Article
- Impact of Chaperone-Mediated Autophagy in Brain Aging: Neurodegenerative Diseases and Glioblastoma.Frontiers in aging neuroscience · 2020Article
- Neuronal p38α mediates age-associated neural stem cell exhaustion and cognitive decline.Aging cell · 2019Article
- Moderate-Intensity Exercise Induces Neurogenesis and Improves Cognition in Old Mice by Upregulating Hippocampal Hippocalcin, Otub1, and Spectrin-α.Molecular neurobiology · 2019Article
- Molecular Mechanisms of Neurogenic Aging in the Adult Mouse Subventricular Zone.Journal of experimental neuroscience · 2019Review
- Turning back time with emerging rejuvenation strategies.Nature cell biology · 2019Review
- Genetic Pathways of Aging and Their Relevance in the Dog as a Natural Model of Human Aging.Frontiers in genetics · 2019Review
- SOX2 haploinsufficiency promotes impaired vision at advanced age.Oncotarget · 2018Article
- Impaired Notch Signaling Leads to a Decrease in p53 Activity and Mitotic Catastrophe in Aged Muscle Stem Cells.Cell stem cell · 2018Article
- Control of metabolism by p53 - Cancer and beyond.Biochimica et biophysica acta. Reviews on cancer · 2018Review
- "Till Death Do Us Part": A Potential Irreversible Link Between Aberrant Cell Cycle Control and Neurodegeneration in the Adult Olfactory Bulb.Frontiers in neuroscience · 2018Review
- rhEPO Enhances Cellular Anti-oxidant Capacity to Protect Long-Term Cultured Aging Primary Nerve Cells.Journal of molecular neuroscience : MN · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The impairment of the activity of the brain is a major feature of aging, which coincides with a decrease in the function of neural stem cells. We have previously shown that an extra copy of regulated Ink4/Arf and p53 activity, in s-Ink4/Arf/p53 mice, elongates lifespan and delays aging. In this work, we examined the physiology of the s-Ink4/Arf/p53 brain with aging, focusing on the neural stem cell (NSC) population. We show that cells derived from old s-Ink4/Arf/p53 mice display enhanced neurosphere formation and self-renewal activity compared with wt controls. This correlates with augmented expression of Sox2, Sox9, Glast, Ascl1, and Ars2 NSC markers in the subventricular zone (SVZ) and in the subgranular zone of the dentate gyrus (DG) niches. Furthermore, aged s-Ink4/Arf/p53 mice express higher levels of Doublecortin and PSA-NCAM (neuroblasts) and NeuN (neurons) in the olfactory bulbs (OB) and DG, indicating increased neurogenesis in vivo. Finally, aged s-Ink4/Arf/p53 mice present enhanced behavioral and neuromuscular coordination activity. Together, these findings demonstrate that increased but regulated Ink4/Arf and p53 activity ameliorates age-related deterioration of the central nervous system activity required to maintain the stem cell pool, providing a mechanism not only for the extended lifespan but also for the health span of these mice.
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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.