biostudies-literatureGureev APStudy of mitochondria oxidative damage and Nrf2 signalingRussian Science Support FoundationStudy of cognitive function of aging miceRussian science foundation15197https://www.ebi.ac.uk/biostudies/studies/S-EPMC9739464biostudies-literatureUnknown23(23)In this research, we compared the cognitive parameters of 2-, 7-, and 15-month-old mice, changes in mitochondrial DNA (mtDNA) integrity and expression of genes involved in the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. We showed an age-related decrease in the <i>Nfe2l2</i> expression in the cerebral cortex, not in the hippocampus. At the same time, we find an increase in the mtDNA copy number in the cerebral cortex, despite the lack of an increase in gene expression, which is involved in the mitochondrial biogenesis regulation. We suppose that increase in mtDNA content is associated with mitophagy downregulation. We supposed that mitophagy downregulation may be associated with an age-related increase in the mtDNA damage. In the hippocampInternational journal of molecular sciencesAge-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments.PMC973946421-75-3000922-74-00115Shaforostova EAPopov VNGureev APCherednichenko VRKhorolskaya VGSadovnikova ISBurakova IYPlotnikov EYfalseAge-Related Decline in Nrf2/ARE Signaling Is Associated with the Mitochondrial DNA Damage and Cognitive Impairments.In this research, we compared the cognitive parameters of 2-, 7-, and 15-month-old mice, changes in mitochondrial DNA (mtDNA) integrity and expression of genes involved in the nuclear erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway. We showed an age-related decrease in the <i>Nfe2l2</i> expression in the cerebral cortex, not in the hippocampus. At the same time, we find an increase in the mtDNA copy number in the cerebral cortex, despite the lack of an increase in gene expression, which is involved in the mitochondrial biogenesis regulation. We suppose that increase in mtDNA content is associated with mitophagy downregulation. We supposed that mitophagy downregulation may be associated with an age-related increase in the mtDNA damage. In the hippocamp2022-01-01T00:00:00Z2022 Dec2025-06-01T01:55:40.017Z2024-11-14T17:44:51.622ZS-EPMC97394643649951710.3390/ijms232315197