PMID:22384090

Citation	Abdouh, M, Chatoo, W, El Hajjar, J, David, J, Ferreira, J and Bernier, G (2012) Bmi1 is down-regulated in the aging brain and displays antioxidant and protective activities in neurons. PLoS ONE 7:e31870
Abstract	Aging increases the risk to develop several neurodegenerative diseases, although the underlying mechanisms are poorly understood. Inactivation of the Polycomb group gene Bmi1 in mice results in growth retardation, cerebellar degeneration, and development of a premature aging-like phenotype. This progeroid phenotype is characterized by formation of lens cataracts, apoptosis of cortical neurons, and increase of reactive oxygen species (ROS) concentrations, owing to p53-mediated repression of antioxidant response (AOR) genes. Herein we report that Bmi1 expression progressively declines in the neurons of aging mouse and human brains. In old brains, p53 accumulates at the promoter of AOR genes, correlating with a repressed chromatin state, down-regulation of AOR genes, and increased oxidative damages to lipids and DNA. Comparative gene expression analysis further revealed that aging brains display an up-regulation of the senescence-associated genes IL-6, p19(Arf) and p16(Ink4a), along with the pro-apoptotic gene Noxa, as seen in Bmi1-null mice. Increasing Bmi1 expression in cortical neurons conferred robust protection against DNA damage-induced cell death or mitochondrial poisoning, and resulted in suppression of ROS through activation of AOR genes. These observations unveil that Bmi1 genetic deficiency recapitulates aspects of physiological brain aging and that Bmi1 over-expression is a potential therapeutic modality against neurodegeneration.
Links	PubMed PMC3285640 Online version:10.1371/journal.pone.0031870
Keywords	Aging; Animals; Antioxidants/metabolism; Apoptosis; Brain/metabolism; Brain/physiology; Chromatin/metabolism; DNA/metabolism; Down-Regulation; Gene Expression Profiling; Gene Expression Regulation; Genes, p53; Humans; Lipid Peroxidation; Lipids/chemistry; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurodegenerative Diseases/metabolism; Neurodegenerative Diseases/prevention & control; Neurons/metabolism; Nuclear Proteins/metabolism; Oxidative Stress; Promoter Regions, Genetic; Proto-Oncogene Proteins/metabolism; Reactive Oxygen Species; Repressor Proteins/metabolism; Tumor Suppressor Protein p53/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:BMI1		GO:0043526: neuroprotection	ECO:0000315:		P		Figure 3. Loss of BM1 due to aging results in loss of neurons	complete CACAO 3901

References

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