Aging brain

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

Contribution of glutamatergic signaling to nitrosative stress-induced protein misfolding in normal brain aging and neurodegenerative diseases.

Abstract: Glutamatergic hyperactivity, associated with Ca2+ influx and consequent production of nitric oxide (NO), is potentially involved in both normal brain aging and age-related neurodegenerative disorders. Many neurodegenerative diseases are characterized by conformational changes in proteins that result in their misfolding and aggregation. Normal protein degradation by the ubiquitin-proteasome system can prevent accumulation of aberrantly folded proteins. Our recent studies have linked nitrosative stress to protein misfolding and neuronal cell death. In particular, molecular chaperones - such as protein disulfide isomerase, glucose regulated protein 78, and heat shock proteins - can provide neuroprotection from misfolded proteins by facilitating proper folding and thus preventing aggregation. Here, we present evidence for the hypothesis that NO contributes to normal brain aging and degenerative conditions by S-nitrosylating specific chaperones that would otherwise prevent accumulation of misfolded proteins.

Heme Oxygenase-1 Activity as a Correlate to Exercise-Mediated Amelioration of Cognitive Decline and Neuropathological Alterations in an Aging Rat Model of Dementia.

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on spatial memory, imaging, and pathological abnormalities. Particular focus has been given to the role of heme oxygenase-1 (HO-1)-an important cellular cytoprotectant in preserving mental acuity-using an aging rat model of dementia. Male and female Wistar rats were segregated into six groups-namely, (i) aged sedentary (control) females (ASF, n = 8); (ii) aged sedentary (control) males (ASM, n = 8); (iii) aged running females (ARF, n = 8); (iv) aged running males (ARM, n = 8); (v) young control females (YCF, n = 8); and (vi) young control males (YCM, n = 8). Rats in the ARF and ARM groups had free access to a standardized inbuilt running wheel during the 3-month evaluation period. Spatial memory was investigated using the Morris Water Test, imaging and pathological alterations were assessed using positron emission tomography (PET) imaging and histopathological examinations (H&E, Congo red staining), respectively, and HO-1 enzyme activity assays were also conducted. The outcomes suggest that voluntary physical exercise mitigates impaired spatial memory and neuropathological changes exhibited by the aging sedentary group, via elevated HO-1 activity, contributing to the antioxidant capacity in the aging brain.

Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

Abstract: Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

Aging-Related Changes in Cognition and Cortical Integrity are Associated With Serum Expression of Candidate MicroRNAs for Alzheimer Disease.

Abstract: Evidence has shown that microRNAs (miRNAs) are involved in molecular pathways responsible for aging and prevalent aging-related chronic diseases. However, the lack of research linking circulating levels of miRNAs to changes in the aging brain hampers clinical translation. Here, we have investigated if serum expression of brain-enriched miRNAs that have been proposed as potential biomarkers in Alzheimer's disease (AD) (miR-9, miR-29b, miR-34a, miR-125b, and miR-146a) are also associated with cognitive functioning and changes of the cerebral cortex in normal elderly subjects. Results revealed that candidate miRNAs were linked to changes in cortical thickness (miR-9, miR-29b, miR-34a, and miR-125b), cortical glucose metabolism (miR-29b, miR-125b, and miR-146a), and cognitive performance (miR-9, miR-34a, and miR-125b). While both miR-29b and miR-125b were related to aging-related structural and metabolic cortical changes, only expression levels of miR-125b were associated with patterns of glucose consumption shown by cortical regions that correlated with executive function. Together, these findings suggest that serum expression of AD-related miRNAs are biologically meaningful in aging and may play a role as biomarkers of cerebral vulnerability in late life.

Modification of cell to cell signals during normal and pathological aging

Abstract: Functional Morphology and Cerebral Metabolism During Normal and Pathological Aging.- Functional morphology of neurons during normal and pathological ageing.- Functional morphology during normal and pathological ageing with emphasis on peptidergic transmission.- P.E.T. study of human brain metabolism in aging and dementia.- An experimental approach to the study of the functional derangement which follows aging of the brain and dementia.- Alzheimer's disease causes metabolic uncoupling of associative brain regions beyond that seen in the healthy elderly.- Neurochemical, Neuroendocrine and Molecular Changes During Aging in Animals and in Man.- Neurotransmitters, genetics and aging.- Neuroendocrine aspects of aging.- The neuronotrophic hypothesis of the aging brain.- Example of age related changes of transducing mechanisms and of cerebral circuits.- Changes in calcium homeostasis during aging.- Dietary and neuroendocrine modulation of age related changes in dopaminergic action during aging.- Dopaminergic system in the aged brain: evidence for a selective loss of D-1 but not D-2 receptors.- Neurotransmitter changes in human brain during ageing.- The influence of age on neurotransmitters in the human brain.- Normal Versus Pathological Aging in Man:.- Senile dementias: an overview.- Growing points of the neurobiology of Alzheimer's disease.- The Alzheimer tangle and aging.- New perspectives in Parkinson's disease.- Guidelines of the care of the aged patients.- Subjective and objective health in aging: problems of assessment.- Drug development in geriatrics.