Nrf2: Molecular and epigenetic regulation during aging |
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| Affiliation: | 1. Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana-Iztapalapa, Ciudad de Mexico, 09340, Mexico;2. Departamento de Biomedicina Cardiovascular, Instituto Nacional de Cardiología-Ignacio Chávez, Ciudad de Mexico, Mexico;3. Posgrado en Biología Experimental, UAM-I, Mexico;1. Department of Biological Sciences, Northern Arizona University, Flagstaff, AZ, United States;2. Department of Chemistry, University of Massachusetts, Lowell, United States;1. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia;2. Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia;3. School of Medical Sciences, University of New South Wales, Sydney, Australia;4. Department of Aged Care and Rehabilitation, Bankstown Hospital, Bankstown, NSW, Australia;5. Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, Australia;1. School of Pharmacy, University of Wisconsin-Madison, WI, USA;2. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, WI, USA;3. Center of Neuroscience, University of Wisconsin-Madison, WI, USA;4. Waisman Center, University of Wisconsin-Madison, WI, USA;1. University of Torino, Department of Oncology, Candiolo Cancer Institute-FPO, IRCCS, Strada Provinciale 142, 10060 Candiolo, Torino, Italy;2. Department of Biomedical Sciences, University of Cagliari, Via Porcell 4, 09124 Cagliari, Italy |
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| Abstract: | Increase in life-span is commonly related with age-related diseases and with gradual loss of genomic, proteomic and metabolic integrity. Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) controls the expression of genes whose products include antioxidant proteins, detoxifying enzymes, drug transporters and numerous cytoprotective proteins. Several experimental approaches have evaluated the potential regulation of the transcription factor Nrf2 to enhance the expression of genes that contend against accumulative oxidative stress and promote healthy aging. Negative regulators of Nrf2 that act preventing it´s binding to DNA-responsive elements, have been identified in young and adult animal models. However, it is not clearly established if Nrf2 decreased activity in several models of aging results from disruption of that regulation. In this review, we present a compilation of evidences showing that changes in the levels or activity of Keap1 (Kelch-like ECH associated protein 1), GSK-3β (glycogen synthase kinase-3), Bach1, p53, Hrd1 (E3 ubiquitin ligase) and miRNAs might impact on Nrf2 activity during elderly. We conclude that understanding Nrf2 regulatory mechanisms is essential to develop a rational strategy to prevent the loss of cellular protection response during aging. |
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| Keywords: | Aging Negative regulation Nrf2 Epigenetic modifications |
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