scholarly journals Endocannabinoid Signaling for GABAergic-Microglia (Mis)Communication in the Brain Aging

2021 ◽  
Vol 14 ◽  
Author(s):  
Jorge Carrera ◽  
Jensen Tomberlin ◽  
John Kurtz ◽  
Eda Karakaya ◽  
Mehmet Bostanciklioglu ◽  
...  
Keyword(s):  
Communication System ◽  
Brain Aging ◽  
Neuronal Loss ◽  
Endocannabinoid System ◽  
Therapeutic Interventions ◽  
Aging Brain ◽  
Age Related ◽  
The Brain ◽  
Excessive Activation ◽  
By Products

The aging brain seems to be characterized by neuronal loss leading to cognitive decline and progressively worsening symptoms related to neurodegeneration. Also, pro-inflammatory states, if prolonged, may increase neuronal vulnerability via excessive activation of microglia and their pro-inflammatory by-products, which is seen as individuals increase in age. Consequently, microglial activity is tightly regulated by neuron-microglia communications. The endocannabinoid system (ECS) is emerging as a regulator of microglia and the neuronal-microglia communication system. Recently, it has been demonstrated that cannabinoid 1 (CB1) receptor signaling on GABAergic interneurons plays a crucial role in regulating microglial activity. Interestingly, if endocannabinoid signaling on GABAergic neurons are disturbed, the phenotypes mimic central nervous system insult models by activating microglia and leading to accelerated brain aging. Investigating the endocannabinoid receptors, ligands, and genetic deletions yields the potential to understand the communication system and mechanism by which the ECS regulates glial cells and aspects of aging. While there remains much to discover with the ECS, the information gathered and identified already could lead to the development of cell-specific therapeutic interventions that help in reducing the effects of age-related pro-inflammatory states and neurodegeneration.

scholarly journals Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10251
Author(s):  
Vladimir Sukhorukov ◽  
Dmitry Voronkov ◽  
Tatiana Baranich ◽  
Natalia Mudzhiri ◽  
Alina Magnaeva ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Aging ◽  
Cellular Level ◽  
Aging Brain ◽  
The Past ◽  
Age Related ◽  
Accumulation Of Damage ◽  
Quantity Control ◽  
The Brain

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

scholarly journals Structure and function of the aging brain

2018 ◽  
Author(s):  
R. Nathan Spreng ◽  
Gary R. Turner
Keyword(s):  
Brain Aging ◽  
American Psychological Association ◽  
Functional Change ◽  
Structure And Function ◽  
Aging Brain ◽  
Adult Lifespan ◽  
Age Related ◽  
Brain Changes ◽  
And Function ◽  
The Brain

In this opening section of the Aging Brain we set the stage for the contributions that follow by providing a broad overview of the latest advances in our understanding of how the brain changes, both structurally and functionally, across the adult lifespan. We leave domain-specific aspects of brain aging to the subsequent chapters, where contributors will provide more targeted accounts of brain change germane to their particular focus on the aging brain. Here we review the extant, and rapidly expanding literature to provide a brief overview and introduction to structural and functional change that occur with typical brain aging. We begin the chapter by looking back, to review some of the early discoveries about how the brain changes across the adult lifespan. We close the chapter by looking forward, towards new discoveries that challenge our core assumptions about the inevitability or irreversibility of age-related brain changes. These sections serve as bookends for the core of the chapter where we review the latest research advances that continue to uncover the mysteries of the aging brain. Spreng, R.N., Turner, G.R. (2019, forthcoming) Structure and function of the aging brain. In G Samanez-Larkin (Ed.) The aging brain. Washington DC: American Psychological Association.

Advances in Our Understanding of the Pathophysiology of Alzheimer’s Disease

US Neurology ◽  
2010 ◽  
Vol 06 (01) ◽  
pp. 28 ◽  
Author(s):  
Kim N Green ◽  
Steven S Schreiber ◽  
◽  
Keyword(s):  
Symptomatic Relief ◽  
Neuronal Loss ◽  
Current Understanding ◽  
Therapeutic Interventions ◽  
Disease Modification ◽  
The Past ◽  
Age Related ◽  
The Us ◽  
Alois Alzheimer ◽  
The Brain

Alzheimer’s disease (AD) is the most common age-related dementia, currently affecting more than 5 million patients in the US alone, and is characterized by the presence of both extracellular plaques and intraneuronal tangles in the brain of a patient with dementia. Alois Alzheimer first described the pathology associated with the disease over 100 years ago, and during the past three decades our understanding of the disease and of potential ways to treat it has increased tremendously. In this article we describe our current understanding of both the pathophysiology of Alzheimer’s disease and current and future therapeutic interventions, including symptomatic relief, disease modification, and the reversal of synaptic and neuronal loss.

scholarly journals Successful brain aging: plasticity, environmental enrichment, and lifestyle

2013 ◽  
Vol 15 (1) ◽  
pp. 45-52 ◽  
Keyword(s):  
Cognitive Deficits ◽  
Successful Aging ◽  
Environmental Enrichment ◽  
Brain Aging ◽  
Memory Loss ◽  
Lifestyle Factors ◽  
Mechanisms Of Action ◽  
Aging Brain ◽  
Age Related ◽  
The Brain

Aging is a physiological process that can develop without the appearance of concurrent diseases. However, very frequently, older people suffer from memory loss and an accelerated cognitive decline. Studies of the neurobiology of aging are beginning to decipher the mechanisms underlying not only the physiology of aging of the brain but also the mechanisms that make people more vulnerable to cognitive dysfunction and neurodegenerative diseases. Today we know that the aging brain retains a considerable functional plasticity, and that this plasticity is positively promoted by genes activated by different lifestyle factors. In this article some of these lifestyle factors and their mechanisms of action are reviewed, including environmental enrichment and the importance of food intake and some nutrients. Aerobic physical exercise and reduction of chronic stress are also briefly reviewed. It is proposed that lifestyle factors are powerful instruments to promote healthy and successful aging of the brain and delay the appearance of age-related cognitive deficits in elderly people.

Changes of the Brain Synapses During Aging. New Aspects

2001 ◽  
Vol 56 (11-12) ◽  
pp. 921-929 ◽  
Author(s):  
Kleopatra Schulpis ◽  
Artemis Doulgeraki ◽  
Stylianos Tsakiris
Keyword(s):  
Successful Aging ◽  
Brain Aging ◽  
Aging Brain ◽  
Compensatory Mechanisms ◽  
Age Related ◽  
Adaptive Mechanisms ◽  
Functional Implications ◽  
Effects Of Aging ◽  
The Brain

Abstract The process of brain aging is an interaction of age-related losses and compensatory mechanisms. This review is focused on the changes of the synaptic number and structure, their functional implications, regarding neurotransmission, as well as the electrical activity of neuronal circuits. Moreover, the importance of calcium homeostasis is strongly emphasized. It is also suggested that many neuronal properties are preserved, as a result of adaptive mechanisms, and that a series of interdependent factors regulate brain aging. The "new fron­ tier" in research is the challenge of understanding the effects of aging, both to prevent degen­ erative diseases and reduce their consequences. New aspects are considered a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral microcirculation, d) m eta­ bolic features of aging brain, e) the possible neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids and e) stress and aging. These numerous multifactorial approaches are essential to understand the process of aging. The more we learn about it, the more we realize how to achieve "successful" aging. M inireview

scholarly journals The Neural Economics of Brain Aging

2021 ◽  
Author(s):  
Jacob Kosyakovsky
Keyword(s):  
Human Brain ◽  
Neurodegenerative Disease ◽  
Brain Function ◽  
Large Scale ◽  
Brain Aging ◽  
Late Onset ◽  
Functional Decline ◽  
Neuronal Loss ◽  
Aging Brain ◽  
Age Related

Abstract Human brain aging is a true spectrum across the population, ranging from minimal changes on the microscopic level to full-blown neurodegenerative disease with accumulation of pathology, neuronal loss, dysfunctional large-scale brain networks, and progressive functional decline. Although much is known about the individual mechanisms involved in brain aging, a convincing framework that ties these highly related processes together is lacking. Herein, using mathematical modeling, I sought to understand decline with brain aging by capturing the essential macro-level processes that shape how a brain changes over the lifetime. I develop ABC (Aging Brain Capital), a simple linear simultaneous-equation model that unites aspects of neuroscience, economics, and thermodynamics to explain the evolution of brain pathology and human brain capital, the infrastructure and processes that underlie brain function, over the lifespan. The results of this model suggest that aging-associated decline in brain function is inevitable, driven by the finite nature of the brain’s pathology-clearance capacity. Furthermore, age-related neurodegenerative diseases can be understood as part of this aging process, explaining the spectrum of pathology and neurodegeneration across the population. I demonstrate that several essential aspects of the pathogenesis of Alzheimer disease (AD) can be likewise explained in this framework incorporating amyloid-tau interaction, the emerging concept that amyloid pathology accelerates tau pathology. The conception of Alzheimer pathogenesis that I present not only explains and unifies the basis for familial AD, primary-age-related tauopathy (PART), and late-onset AD (LOAD), but also reconciles amyloid-centered, tau-centered, and synergistic models of AD. Finally, I describe the possible implications of these results for future therapeutic development across neurodegenerative disease.

scholarly journals Impairments in Brain Bioenergetics in Aging and Tau Pathology: A Chicken and Egg Situation?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2531
Author(s):  
Amandine Grimm
Keyword(s):  
Brain Metabolism ◽  
Brain Aging ◽  
Cognitive Impairments ◽  
Tau Phosphorylation ◽  
The Body ◽  
Tau Pathology ◽  
Age Related ◽  
Energy Consuming ◽  
Effects Of Aging ◽  
The Brain

The brain is the most energy-consuming organ of the body and impairments in brain energy metabolism will affect neuronal functionality and viability. Brain aging is marked by defects in energetic metabolism. Abnormal tau protein is a hallmark of tauopathies, including Alzheimer’s disease (AD). Pathological tau was shown to induce bioenergetic impairments by affecting mitochondrial function. Although it is now clear that mutations in the tau-coding gene lead to tau pathology, the causes of abnormal tau phosphorylation and aggregation in non-familial tauopathies, such as sporadic AD, remain elusive. Strikingly, both tau pathology and brain hypometabolism correlate with cognitive impairments in AD. The aim of this review is to discuss the link between age-related decrease in brain metabolism and tau pathology. In particular, the following points will be discussed: (i) the common bioenergetic features observed during brain aging and tauopathies; (ii) how age-related bioenergetic defects affect tau pathology; (iii) the influence of lifestyle factors known to modulate brain bioenergetics on tau pathology. The findings compiled here suggest that age-related bioenergetic defects may trigger abnormal tau phosphorylation/aggregation and cognitive impairments after passing a pathological threshold. Understanding the effects of aging on brain metabolism may therefore help to identify disease-modifying strategies against tau-induced neurodegeneration.

scholarly journals Electrophysiological signatures of brain aging in autism spectrum disorder

2021 ◽  
Author(s):  
Abigail Dickinson ◽  
Shafali Jeste ◽  
Elizabeth Milne
Keyword(s):  
Autism Spectrum Disorder ◽  
Brain Aging ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Aging Brain ◽  
Significant Group ◽  
Care Plans ◽  
Alpha Frequency ◽  
Age Related ◽  
Adults With Asd

AbstractEmerging evidence suggests that aging processes may be altered in adults with autism spectrum disorder (ASD). However, it remains unclear if oscillatory slowing, a key neurophysiological change in the aging brain, manifests atypically in this population. This study sought to examine patterns of age-related oscillatory slowing in adults with ASD, captured by reductions in the brain’s peak alpha frequency. Resting-state EEG data from adults (18-70 years) with ASD (N=93) and age-matched neurotypical (NT) controls (N=87) were pooled from three independent datasets. A robust curve-fitting procedure quantified the peak frequency of alpha oscillations (7-13Hz) across all brain regions. Associations between peak alpha frequency and age were assessed and compared between groups. Consistent with characteristic patterns of oscillatory slowing, peak alpha frequency was negatively associated with age across the entire sample (p<.0001). A significant group by age interaction revealed that this relationship was more pronounced in adults with ASD (p<.01), suggesting that that age-related oscillatory slowing may be accelerated in this population. Scalable EEG measures such as peak alpha frequency could provide insights into neural aging that are crucially needed to inform care plans and preventive interventions that can promote successful aging in ASD.

scholarly journals The aging mind: neuroplasticity in response to cognitive training

2013 ◽  
Vol 15 (1) ◽  
pp. 109-119 ◽  
Keyword(s):  
Cognitive Function ◽  
Cognitive Training ◽  
Neural Plasticity ◽  
Cognitive Effort ◽  
Aging Brain ◽  
Cognitive Domains ◽  
Training Techniques ◽  
Age Related ◽  
Strategy Change ◽  
The Brain

Is it possible to enhance neural and cognitive function with cognitive training techniques? Can we delay age-related decline in cognitive function with interventions and stave off Alzheimer's disease? Does an aged brain really have the capacity to change in response to stimulation? In the present paper, we consider the neuroplasticity of the aging brain, that is, the brain's ability to increase capacity in response to sustained experience. We argue that, although there is some neural deterioration that occurs with age, the brain has the capacity to increase neural activity and develop neural scaffolding to regulate cognitive function. We suggest that increase in neural volume in response to cognitive training or experience is a clear indicator of change, but that changes in activation in response to cognitive training may be evidence of strategy change rather than indicative of neural plasticity. We note that the effect of cognitive training is surprisingly durable over time, but that the evidence that training effects transfer to other cognitive domains is relatively limited. We review evidence which suggests that engagement in an environment that requires sustained cognitive effort may facilitate cognitive function.

Aging

2019 ◽  
pp. 105-112
Author(s):  
Risto Näätänen ◽  
Teija Kujala ◽  
Gregory Light
Keyword(s):  
Hearing Loss ◽  
Speech Perception ◽  
Cognitive Decline ◽  
Temporal Processing ◽  
Brain Aging ◽  
Brain Plasticity ◽  
Part Of Speech ◽  
Memory Traces ◽  
Age Related ◽  
The Brain

This chapter shows that MMN and its magnetoencephalographic (MEG) equivalent MMNm are sensitive indices of aging-related perceptual and cognitive decline. Importantly, the age-related neural changes are associated with a decrease of general brain plasticity, i.e. that of the ability of the brain to form and maintain sensory-memory traces, a necessary basis for veridical perception and appropriate cognitive brain function. MMN/MMNm to change in stimulus duration is particularly affected by aging, suggesting the increased vulnerability of temporal processing to brain aging and accounting, for instance, for a large part of speech-perception difficulties of the aged beyond the age-related peripheral hearing loss.

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