Aging brain

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

Reactive Oxygen Involvement in Neurodegenerative Pathways

Abstract: As organs age, the likelihood of severe dysfunction increases steadily. The brain is particularly sensitive to age-related, chronic and acute oxidative pathologies. An emerging paradigm holds that diverse neurodegenerative conditions share a common etiological factor, namely, enhanced brain tissue oxidation owing to exacerbated production of reactive oxygen species (ROS) or to compromise of antioxidant defense and repair mechanisms. Brain is particularly susceptible to oxidative stress owing to its high content of unsaturated lipids, high metabolic rate, relative dearth of antioxidant enzymes, and inability to regenerate lost neurons. Pathogenic ROS generation may result from metabolic enzyme dysregulation, impaired mitochondrial respiration, excitotoxic stimulation, and secondarily as a function of intracellular calcium stress (summarized in Fig. 1 and elaborated below). Natural variation in antioxidant systems may explain why humans differ so greatly with respect to pathways and rates of neurodegeneration. If this is the case, antioxidant supplementation of the aging brain may forestall certain aspects of age-related neurodegeneration. Accordingly, much research has focused on antioxidant management of aging brain and on antioxidant interdiction of postischemic brain damage. Recent findings indicate that specific antioxidants do more than scavenge ROS, but may indirectly affect cellular signal transduction, genetic response, and inflammatory events in such a way as to modulate beneficially brain response to oxidative challenge.

Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer's Disease.

Abstract: The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer's disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. Specifically, we focus on pharmacological treatment (e.g., rapamycin) for restoring brain functions in animals modeling human AD; nutritional interventions (e.g., CR and ketogenic diet) for enhancing brain vascular and metabolic functions in rodents at young age (5-6 months of age) and preserving those functions in aging (18-20 months of age). Various magnetic resonance (MR) methods [i.e., imaging (MRI), angiography (MRA), and spectroscopy (MRS)], confocal microscopic imaging, and positron emission tomography (PET) provided in vivo metabolic and vascular measures. We also discuss the translational potential of mTOR interventions. Since PET and various MR neuroimaging methods, as well as the different interventions (e.g., rapamycin, CR, and ketogenic diet) are also available for humans, these findings may have tremendous implications in future clinical trials of neurological disorders in aging populations.

Molecular neuropathology of aging

Abstract: This book contains over 30 selections. Some of the titles are: Physiological Approaches to the Roles of Gene Regulation in the Brain during Aging; Isolation of a cDNA Clone Encoding the Alzheimer's Disease and Down's Syndrome Amyloid Peptide; Isolation, Characterization, and Chromosomal Localization of a human brain cDNA clone coding for the amyloid BETA-protein Found in Alzheimer's Disease, Down's Syndrome, and Aging Brain; and Genetic Linkage Analysis of Familial Alzheimer's Disease.

Increased Hippocampal Excitability and Altered Learning Dynamics Mediate Cognitive Mapping Deficits in Human Aging.

Abstract: Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment (VE). We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex (RSC)/parieto-occipital sulcus (POS) and anterior hippocampus did not change systematically as a function learning in older compared with younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects computations in the brain's navigation system, highlighting the critical role of the hippocampus.SIGNIFICANCE STATEMENT Key structures of the brain's navigation circuit are particularly vulnerable to the deleterious consequences of aging, and declines in spatial navigation are among the earliest indicators for a progression from healthy aging to neurodegenerative diseases. Our study is among the first to provide a mechanistic account about how physiological changes in the aging brain affect the formation of spatial knowledge. We show that neural activity in the aging hippocampus and medial parietal areas is decoupled from individual learning states across repeated episodes in a novel spatial environment. Importantly, we find that increased excitability of the anterior hippocampus might constitute a potential neural mechanism for cognitive mapping deficits in old age.