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Aging brain
About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.
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TL;DR: Several different types of mechanisms appear to be important in RNA and protein metabolism of the brain during aging, but selectivity for brain region and cell type seems to prevail throughout these myriad changes.
Abstract: Much work in the molecular neurobiology of aging is still necessarily descriptive, pending more data on the relative contributions of neuron loss vs. neuron atrophy and glial hyperactivity during normal and neuropathological aging. Major loss of neuronal cells is not the rule, even in AD. A working hypothesis holds that increased astrocytic volumes and decreased neuronal volumes are a major factor in age-related neurochemical decreases. Resolution of these questions is needed to understand how regional RNA and protein synthesis change during aging. We have presented alternative mechanisms for changes in gene expression that may be cell specific. The literature, mainly from non-neural tissues, suggests derepression of normally silent genes, possibly in association with DNA demethylation; decreased synthesis of neuronal rRNA due to deletion of rRNA genes; epigenetic changes in hnRNA splicing; reduced turnover rates and the accumulation of nonfunctional proteins. Although global qualitative changes in the inventory of mRNA and proteins are not found in neural tissues at advanced ages, the synthesis and turnover of RNA and protein may be slowed. Impaired protein turnover or catabolism could contribute to the accumulation of NFT and brain amyloid. In sum, several different types of mechanisms appear to be important in RNA and protein metabolism of the brain during aging, but selectivity for brain region and cell type seems to prevail throughout these myriad changes.
80 citations
TL;DR: This study supports the view that intense exercise above the lactate threshold may benefit the aging brain and suggests supra-lactate threshold exercise activates a partial mitochondrial biogenesis in aged mice, and a gene known to support neurogenesis.
79 citations
TL;DR: In this paper, the authors reported robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability, which was subdued by global inactivation and by endothelial cell-specific ablation of C3ar1.
Abstract: Dysfunction of immune and vascular systems has been implicated in aging and Alzheimer disease; however, their interrelatedness remains poorly understood. The complement pathway is a well-established regulator of innate immunity in the brain. Here, we report robust age-dependent increases in vascular inflammation, peripheral lymphocyte infiltration, and blood-brain barrier (BBB) permeability. These phenotypes were subdued by global inactivation and by endothelial cell-specific ablation of C3ar1. Using an in vitro model of the BBB, we identified intracellular Ca2+ as a downstream effector of C3a/C3aR signaling and a functional mediator of vascular endothelial cadherin junction and barrier integrity. Endothelial C3ar1 inactivation also dampened microglia reactivity and improved hippocampal and cortical volumes in the aging brain, demonstrating a crosstalk between brain vasculature dysfunction and immune cell activation and neurodegeneration. Further, prominent C3aR-dependent vascular inflammation was also observed in a tau-transgenic mouse model. Our studies suggest that heightened C3a/C3aR signaling through endothelial cells promotes vascular inflammation and BBB dysfunction and contributes to overall neuroinflammation in aging and neurodegenerative disease.
79 citations
TL;DR: The introduction of autoradiographic methods to study quantitatively the relative amounts of nDNA damage and nDNA repair on tissue sections revealed a formerly unknown inverse relationship between age-related accumulation of n DNA damage and age- related impairment in n DNA repair on the one hand, and theAge-related, selective, loss of neurons on the other hand.
79 citations
TL;DR: Stereologic investigations of nerve cells in the brain cortex and putamen revealed that only in brains over 85 years of age can a significant decrease in nerve cell size be demonstrated, which suggests a functional interaction between the nerve cells and the capillaries.
78 citations