Aging brain

About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.

Oxidative Damage to the TCA Cycle Enzyme MDH1 Dysregulates Bioenergetic Enzymatic Activity in the Aged Murine Brain.

Abstract: Aging can have profound effects on the mammalian brain leading to neurodegeneration and cognitive impairment. The brain has exceptionally high-energy requirements and is particularly susceptible to damage within its bioenergetic pathways. Here, we asked how the bioenergetic proteome of the murine brain changed with age and how this might affect brain function. Using label-free LC-MS/MS proteomics for the discovery phase and quantitative multiple reaction monitoring LC-MRM-MS/MS for the validation phase, we found dysregulated expression of multiple components of the tricarboxylic acid cycle, which is key for mitochondrial energy production, including SULA2, IDH1, IDH2, SDHB, PDHB, MDH1, FH1, and NDUFS3, in old murine brains. We also saw that the oxidoreductases, thioredoxin and glutaredoxin, were significantly down-regulated in the old mouse brain and showed through MS that this correlated with the accumulation of trioxidation in the key metabolic enzyme MDH1 at Cys137. 3D modeling of MDH1 predicted that the damaged sites were located at the protein active zone, and enzymatic kinetic analysis confirmed that MDH1 function was significantly reduced in the old mouse brain. These findings identify the tricarboxylic acid cycle as a key target of degenerative protein modifications with deleterious effects on the aging brain's bioenergetic function.

Taxifolin retards the D-galactose-induced aging process through inhibiting Nrf2-mediated oxidative stress and regulating the gut microbiota in mice.

Abstract: Aging and aging-related metabolic complications are global problems that seriously threaten public health. Taxifolin (TAX) is a novel health food and has been widely proved to have a variety of biological activities used in food and medicine. However, the delayed effect of TAX on the aging process has not been investigated. The purpose of this study is to explore the role of TAX as a natural active substance on aging brain tissue induced by D-galactose (D-Gal) and to determine the effect of supplementing TAX on the metabolism of the intestinal flora in aging bodies. The aging model was established by intraperitoneal injection of D-Gal (800 mg kg−1) once per 3 days for 12 weeks, and TAX (20 and 40 mg kg−1) was administered daily by oral gavage after 6 weeks of induction with D-Gal. After testing aging mice in an eight-arm maze, the results showed that TAX treatment significantly restored spatial learning and memory impairment. Moreover, long-term D-Gal treatment incited cholinergic dysfunction of aging mice, and H&E staining revealed obvious histopathological damage and structural disorder in the hippocampus of mouse brain tissue, while TAX treatment significantly reversed these changes. Importantly, supplementing with TAX significantly mitigated oxidative stress injury by alleviating the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) while increasing antioxidant enzymes. Furthermore, TAX decreased the apoptosis of the aging brain by regulating the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and activating nuclear factor-erythroid 2-related factor 2 (Nrf2), nuclear heme oxygenase-1 (HO-1), and NADH dehydrogenase quinone 1 (NQO1) to maximally moderate the oxidative stress injury that occurred after D-Gal induction. In addition, 16S rDNA analysis revealed that TAX treatment decelerated the D-gal-induced aging process by regulating the composition of the intestinal flora and abundance of beneficial bacteria, including Enterorhabdus, Clostridium, Bifidobacterium, and Parvibacter. In conclusion, the results of this study demonstrated that TAX alleviated oxidative stress injury in mice aged by D-Gal and also confirmed that TAX improved the aging process by regulating intestinal microbes, which provides the possibility of prevention and treatment for aging and metabolic disorders through the potential food health factors.

Enriched Environment and White Matter in Aging Brain

Abstract: Normal aging is commonly associated with decreased cognitive functions, which could be conspicuously alleviated by enriched environment (EE) with physical, social, and sensory stimuli, suggesting that aging brain still has intriguing plasticity. Multiple researches have been carried out to explore the structural and the molecular changes in aging brain, which would be considered for evidences that EE regulated brain plasticity. Because there is no significant neuron loss in aging cerebral cortex and the white matter is crucial for cognitive functions, this review focused on the age-related white matter changes and the effects of EE on aged white matter. Data from our stereology laboratory revealed that age-related spatial memory declines had more to do with white matter alterations, which were due to marked demyelination and loss of oligodendrocytes in the white matter. We also demonstrated that EE recovered spatial memory impairment and increased white matter volume by promoting marked remyelination in aged brain. This review approached the issue that EE might contribute to normal aging and be beneficial for those suffering from demyelinated diseases.