Aging brain

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

Aging in the Brain: New Roles of Epigenetics in Cognitive Decline.

Abstract: Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA. Furthermore, small non-coding RNA, termed microRNA (miRNA) bind to messenger RNA (mRNA) to regulate translation. In this review, we examine key questions concerning epigenetic mechanisms in regulating the expression of genes associated with brain aging and age-related cognitive decline. In addition, we highlight the interaction of epigenetics with senescent physiology and environmental factors in regulating transcription.

Preferential degradation of cognitive networks differentiates Alzheimer's disease from ageing

Abstract: Converging evidence from structural, metabolic and functional connectivity MRI suggests that neurodegenerative diseases, such as Alzheimer's disease, target specific neural networks. However, age-related network changes commonly co-occur with neuropathological cascades, limiting efforts to disentangle disease-specific alterations in network function from those associated with normal ageing. Here we elucidate the differential effects of ageing and Alzheimer's disease pathology through simultaneous analyses of two functional connectivity MRI datasets: (i) young participants harbouring highly-penetrant mutations leading to autosomal-dominant Alzheimer's disease from the Dominantly Inherited Alzheimer's Network (DIAN), an Alzheimer's disease cohort in which age-related comorbidities are minimal and likelihood of progression along an Alzheimer's disease trajectory is extremely high; and (ii) young and elderly participants from the Harvard Aging Brain Study, a cohort in which imaging biomarkers of amyloid burden and neurodegeneration can be used to disambiguate ageing alone from preclinical Alzheimer's disease. Consonant with prior reports, we observed the preferential degradation of cognitive (especially the default and dorsal attention networks) over motor and sensory networks in early autosomal-dominant Alzheimer's disease, and found that this distinctive degradation pattern was magnified in more advanced stages of disease. Importantly, a nascent form of the pattern observed across the autosomal-dominant Alzheimer's disease spectrum was also detectable in clinically normal elderly with clear biomarker evidence of Alzheimer's disease pathology (preclinical Alzheimer's disease). At the more granular level of individual connections between node pairs, we observed that connections within cognitive networks were preferentially targeted in Alzheimer's disease (with between network connections relatively spared), and that connections between positively coupled nodes (correlations) were preferentially degraded as compared to connections between negatively coupled nodes (anti-correlations). In contrast, ageing in the absence of Alzheimer's disease biomarkers was characterized by a far less network-specific degradation across cognitive and sensory networks, of between- and within-network connections, and of connections between positively and negatively coupled nodes. We go on to demonstrate that formalizing the differential patterns of network degradation in ageing and Alzheimer's disease may have the practical benefit of yielding connectivity measurements that highlight early Alzheimer's disease-related connectivity changes over those due to age-related processes. Together, the contrasting patterns of connectivity in Alzheimer's disease and ageing add to prior work arguing against Alzheimer's disease as a form of accelerated ageing, and suggest multi-network composite functional connectivity MRI metrics may be useful in the detection of early Alzheimer's disease-specific alterations co-occurring with age-related connectivity changes. More broadly, our findings are consistent with a specific pattern of network degradation associated with the spreading of Alzheimer's disease pathology within targeted neural networks.

Brain neurotransmitters in aging and dementia: similar changes across diagnostic dementia groups.

Abstract: Reductions of the levels of transmitter substances and of the activities of enzymes involved in their synthesis have been demonstrated in the aging brain. The sensitivity to the aging process varies for different transmitters and brain regions. Dopamine neurons are more age-sensitive than most other neurons investigated. The metabolism of monoaminergic neurotransmitters is enhanced in the aging brain, as evidenced by increased metabolite/neurotransmitter ratios, perhaps to compensate for the loss of transmitter. In various types of dementia, including Alzheimer's disease (AD) and senile dementia of Alzheimer type (SDAT), several neurotransmitter indices are reduced, as compared to age-matched controls. Moreover, a decrease in neurotransmitter metabolites suggests that compensatory mechanisms are insufficient. No correlation could be found between the neurotransmitter changes and the histological changes characteristic of AD (senile plaques and neurofibrillary tangles). Neither could any relationship between multiple infarctions and neurotransmitter indices be detected. Recently observed changes in the lipid composition of the white matter, indicating demyelinization, in the brains of patients with AD/SDAT, emphasize the multifactorial aspects of dementia. Taken together, the data underline the difficulties in drawing clear demarcation lines between normal and pathological aging and between different subgroups of dementia. Despite the obvious difficulties, future therapeutic efforts should aim at substitution for the neurotransmitter deficiencies. Preventive measures have to await the clarification of the mechanisms underlying neural degeneration. Studies of the toxicity of oxygen and of autoxidation products are among the areas of research that may help to shed light on this problem.

Aging and Cell Structure

Abstract: 1. Central Nervous System.- 1. Introduction.- 2. Dendritic Changes.- 3. Loss of Neurons.- 4. Changes in Dendritic Spines.- 5. Changes in Synaptic Populations.- 6. Changes in Cell Body and Nuclear Sizes.- 7. Changes in Nucleoplasm.- 8. Changes in Neuronal Cytoplasm.- 9. Neurofibrillary Tangles.- 10. Lipofuscin.- 11. Neuroglia.- 12. Choroid Plexus.- References.- 2. The Mammalian Peripheral Nervous System in Old Age.- 1. Introduction.- 2. Age-Related Changes in Man.- 2.1. General Comments.- 2.2. The Aging Sensory Unit.- 2.3. The Aging Motor Unit.- 2.4. The Aging Peripheral Autonomic System.- 2.5. The Aging Peripheral Nerve of Man.- 3. Age-Related Changes in Animals.- 3.1. General Comments.- 3.2. The Aging Sensory Unit.- 3.3. The Aging Motor Unit.- 3.4. The Aging Peripheral Autonomic System.- 3.5. The Aging Peripheral Nerve of Laboratory Animals.- 4. Concluding Remarks.- 4.1. Lipofuscin.- 4.2. Central-Peripheral Distal Axonopathy.- 4.3. Proximal Demyelination.- 4.4. Neuronal Loss.- 4.5. Epilogue.- References.- 3. Neurofibrillary and Synaptic Pathology in the Aged Brain.- 1. Age-Associated Changes in the Human Brain.- 2. Neurofibrillary Pathology.- 2.1. Normal Fibrillar Proteins in the CNS.- 2.2. Neurofibrillary Changes.- 2.3. Experimentally Induced and Naturally Occurring Neurofibrillary Changes.- 3. Synaptic Pathology and Glial Reactions.- 3.1. Morphology of the Neuritic Plaque.- 3.2. Pathogenesis of the Neuritic Plaque.- 3.3. Morphology of the Neuritic Changes.- 3.4. Role of Microglial Cells in Amyloid Deposition.- 3.5. Relationships between Amyloid Fibrils and PHFs.- References.- 4. Cytomorphological Alterations in the Aging Animal Brain with Emphasis on Golgi Studies.- 1. Introduction.- 1.1. The Use of Animal Models in Aging Research.- 1.2. Memory Deficits in Aging Animals.- 1.3. Neuronal Loss in Aging.- 2. The Aging Brain: A Golgi Perspective.- 2.1. The Dendritic Tree and Its Spines.- 2.2. A Survey of Golgi-Impregnated Neuronal Changes in the Aging Cerebral Cortex.- 2.3. Age-Related Alterations in the Cerebellum-Purkinje Cells.- 2.4. Golgi Studies of Dendritic Plasticity in the Adult and Aged Brain.- 3. Electron Microscopy of the Aging Brain.- 3.1. Lipofuscin.- 3.2. Nuclear Membrane Infolding.- 3.3. Filamentous Accumulation.- 3.4. Corpora Amylacea.- 3.5. Synaptic Alterations.- 3.6. Tubulovesicular Profiles.- 3.7. Alterations in Myelinated Fibers.- 4. Discussion.- 4.1. Golgi Studies.- 4.2. Electron Microscopy-Structural Changes in Aging Animal Brain.- 5. Summary and Conclusions.- References.- 5. Variation: Principles and Applications in the Study of Cell Structure and Aging.- 1. Origin of Variation.- 2. Analysis of Variation.- 3. Variation and Aging.- 4. Applications.- 4.1. Variation in Mouse Liver Cellular and Fine Structure: Effects of Aging, Alcohol, and Antioxidants.- 4.2. Variation in Vitality and Mortality.- 4.3. Time-Condensing in Experimental Aging Research through the Study of Variation.- 5. Concluding Remarks.- References.- 6. Ultrastructure of the Aging Kidney.- 1. Introduction.- 2. Materials and Methods.- 2.1. Rats.- 2.2. Humans.- 2.3. Ultrastructural Studies.- 3. Results.- 3.1. Rat Ultrastructural Studies.- 3.2. Clinicopathologic Correlations.- 4. Discussion.- References.- 7. Electron Microscopy of Skeletal Aging.- 1. Introduction.- 2. Bone 252.- 2.1. Periosteum.- 2.2. Endosteum.- 2.3. Osteocytes.- 2.4. Osteoclasts.- 2.5. Bone Surfaces.- 3. Cartilage.- 3.1. General Cartilage Aging.- 3.2. Electron Microscopy of Aging Cartilage.- 4. Summary and Conclusions.- References.- 8. The Cardiovascular System.- 1. Introduction.- 2. The Effect of Age on Physiological Parameters of the Cardiovascular System.- 2.1. Heart Rate and Electrocardiogram.- 2.2. Blood Pressure.- 2.3. Cardiac Output and Stroke Volume.- 2.4. Contractile Properties.- 2.5. Decline of Physical Work Capacity.- 3. The Effect of Age on the Structure of the Myocardium.- 3.1. Connective Tissue.- 3.2. Myocardial Cell.- 4. The Effect of Age on Coronary Vessels.- 5. The Effect of Age on the Reactivity of the Cardiovascular System to Drugs.- 5.1. Age-Associated Changes in Pharmacokinetics of Drugs.- 5.2. Digitalis Glycosides.- 5.3. Autonomic Drugs.- 5.4. Antiarrhythmic Agents.- 6. Summary.- References.- 9. Fine Structure of Aging Skeletal Muscle.- 1. Introduction.- 2. Structural Changes in Human Muscle.- 3. Freeze-Fracture Studies.- References.- 10. Insect vs. Mammalian Aging.- 1. Introduction.- 2. Comparison of Tissue and Body Organization in Insects and Mammals.- 3. Fine Structural Manifestations of Aging.- 3.1. Age Pigment.- 3.2. Mitochondria.- 3.3. Ribosomes, Endoplasmic Reticulum Membranes, and RNA.- 3.4. Nuclei.- 4. Comparison between Insect and Mammalian Aging.- 5. Conclusions.- References.