scholarly journals The neural economics of brain aging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jacob Kosyakovsky
Keyword(s):  
Brain Aging ◽  
Simultaneous Equation ◽  
Equation Model ◽  
Aging Brain ◽  
Human Lifespan ◽  
Linear Simultaneous Equation ◽  
Brain Changes ◽  
Changes Over Time ◽  
The Brain ◽  
Resource Budget

AbstractDespite remarkable advances, research into neurodegeneration and Alzheimer Disease (AD) has nonetheless been dominated by inconsistent and conflicting theory. Basic questions regarding how and why the brain changes over time remain unanswered. In this work, we lay novel foundations for a consistent, integrated view of the aging brain. We develop neural economics—the study of the brain’s infrastructure, brain capital. Using mathematical modeling, we create ABC (Aging Brain Capital), a simple linear simultaneous-equation model that unites aspects of neuroscience, economics, and thermodynamics to explain the rise and fall of brain capital, and thus function, over the human lifespan. Solving and simulating this model, we show that in each of us, the resource budget constraints of our finite brains cause brain capital to reach an upper limit. The thermodynamics of our working brains cause persistent pathologies to inevitably accumulate. With time, the brain becomes damaged causing brain capital to depreciate and decline. Using derivative models, we suggest that this endogenous aging process underpins the pathogenesis and spectrum of neurodegenerative disease. We develop amyloid–tau interaction theory, a paradigm that bridges the unnecessary conflict between amyloid- and tau-centered hypotheses of AD. Finally, we discuss profound implications for therapeutic strategy and development.

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.

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.

Normal Sleep in Childhood

2021 ◽  
pp. 33-48
Author(s):  
Hovig K. Artinian ◽  
Mary Anne Tablizo ◽  
Manisha Witmans
Keyword(s):  
Eye Movement ◽  
Nrem Sleep ◽  
Rapid Eye Movement ◽  
Respiratory Parameters ◽  
Normal Sleep ◽  
Brain Changes ◽  
And Behavior ◽  
Changes Over Time ◽  
The Brain ◽  
Critical Process

Sleep is a critical process in children in that it influences all aspects of physiological functioning, development, and behavior. The two types of sleep, rapid eye movement (REM) sleep and non–rapid eye movement (NREM) sleep, are inherent throughout life; however, the sleep architecture and sleep duration changes over time as the brain changes from the newborn period to adulthood. There are hallmarks related to sleep architectural changes that are specific and unique to the different age ranges. Although the process and neuromodulation of sleep is similar across the life span, there are attributes that are different in children compared to adults. There are also physiological differences in the brain waves and changes in respiratory parameters. This chapter highlights normal sleep in children.

scholarly journals Characterisation of k-Class estimation in simultaneous equation models

1969 ◽  
Vol 74 (3) ◽  
pp. 307-310
Author(s):  
José F. Burguete ◽  
Esteban Burguete
Keyword(s):  
Estimation Method ◽  
Simultaneous Equation ◽  
Equation Model ◽  
Geometric Characterization ◽  
Simultaneous Equation Model ◽  
Oblique Projector ◽  
Linear Simultaneous Equation ◽  
Whole Space ◽  
Simultaneous Equation Models

This paper presents the direct geometric characterization of the k-Class estimation method in a linear simultaneous equation model. The concept of oblique projector is used. The paper also exhibits several estimators generated by projecting along subspaces of the whole space along which this class is projected.

scholarly journals Elevating acetyl-CoA levels reduces aspects of brain aging

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Antonio Currais ◽  
Ling Huang ◽  
Joshua Goldberg ◽  
Michael Petrascheck ◽  
Gamze Ates ◽  
...  
Keyword(s):  
Brain Aging ◽  
Aging Brain ◽  
Acetyl Coa Carboxylase ◽  
Acetyl Coa ◽  
Memory Enhancement ◽  
Drug Candidates ◽  
Mitochondrial Homeostasis ◽  
A Site ◽  
Samp8 Mice ◽  
The Brain

Because old age is the greatest risk factor for dementia, a successful therapy will require an understanding of the physiological changes that occur in the brain with aging. Here, two structurally distinct Alzheimer's disease (AD) drug candidates, CMS121 and J147, were used to identify a unique molecular pathway that is shared between the aging brain and AD. CMS121 and J147 reduced cognitive decline as well as metabolic and transcriptional markers of aging in the brain when administered to rapidly aging SAMP8 mice. Both compounds preserved mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism. CMS121 and J147 increased the levels of acetyl-CoA in cell culture and mice via the inhibition of acetyl-CoA carboxylase 1 (ACC1), resulting in neuroprotection and increased acetylation of histone H3K9 in SAMP8 mice, a site linked to memory enhancement. These data show that targeting specific metabolic aspects of the aging brain could result in treatments for dementia.

Metabolic triad in brain aging: mitochondria, insulin/IGF-1 signalling and JNK signalling

2013 ◽  
Vol 41 (1) ◽  
pp. 101-105 ◽  
Author(s):  
Fei Yin ◽  
Tianyi Jiang ◽  
Enrique Cadenas
Keyword(s):  
Functional Outcomes ◽  
Redox Regulation ◽  
Brain Aging ◽  
Second Messengers ◽  
Cell Signalling ◽  
Signalling Pathways ◽  
Aging Brain ◽  
Phosphatidylinositol 3 Kinase ◽  
The Brain ◽  
Kinase Pathway

Mitochondria generate second messengers, such as H2O2, that are involved in the redox regulation of cell signalling and their function is regulated by several cytosolic signalling pathways. IIS [insulin/IGF1 (insulin-like growth factor 1) signalling] in the brain proceeds mainly through the PI3K (phosphatidylinositol 3-kinase)–Akt (protein kinase B) pathway, which is involved in the regulation of synaptic plasticity and neuronal survival via the maintenance of the bioenergetic and metabolic capacities of mitochondria. Conversely, the JNK (c-Jun N-terminal kinase) pathway is induced by increased oxidative stress and JNK translocation to the mitochondrion results in impairment of energy metabolism. Moreover, IIS and JNK signalling interact with and antagonize each other. This review focuses on functional outcomes of a metabolic triad that entails the co-ordination of mitochondrial function (energy transducing and redox regulation), IIS and JNK signalling, in the aging brain and in neurodegenerative disorders, such as Alzheimer's disease.

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 Functional architecture of the aging brain

2021 ◽  
Author(s):  
Roni Setton ◽  
Laetitia Mwilambwe-Tshilobo ◽  
Manesh Girn ◽  
Amber W. Lockrow ◽  
Giulia Baracchini ◽  
...  
Keyword(s):  
Older Adults ◽  
Functional Connectivity ◽  
Cognitive Aging ◽  
Brain Aging ◽  
Connectivity Pattern ◽  
Aging Brain ◽  
Functional Architecture ◽  
Older Adulthood ◽  
Methodological Challenges ◽  
The Brain

The intrinsic network architecture of the brain is continuously shaped by biological and behavioral factors from younger to older adulthood. Differences in functional networks can reveal how a lifetime of learning and lived experience can alter large-scale neurophysiological dynamics, offering a powerful lens into brain and cognitive aging. Quantifying these differences has been hampered by significant methodological challenges. Here, we use multi-echo fMRI and multi-echo ICA processing, individualized cortical parcellation methods, and multivariate (gradient and edge-level) functional connectivity analyses to provide a definitive account of the intrinsic functional architecture of the brain in older adulthood. Twenty minutes of resting-state multi-echo fMRI data were collected in younger (n=181) and older (n=120) adults. Dimensionality, the number of independent, non-noise BOLD components in the fMRI signal, was significantly reduced for older adults. Macroscale functional gradients were largely preserved. In contrast, edge-level functional connectivity was significantly altered. Within-network connections were weaker while connections between networks were stronger for older adults, and this connectivity pattern was associated with lower executive control functioning. Greater integration of sensory and motor regions with transmodal association cortices also emerged as a prominent feature of the aging connectome. These findings implicate network dedifferentiation, reflected here as reduced dimensionality within the BOLD signal and altered edge-level connectivity, as a global and putatively maladaptive feature of functional brain aging. However, greater coherence among specific networks may also signal adaptive functional reorganization in later life. By overcoming persistent and pervasive methodological challenges that have confounded previous research, the results provide a comprehensive account of the intrinsic functional architecture of the aging brain.

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.

scholarly journals Cellular Senescence in Brain Aging

2021 ◽  
Vol 13 ◽  
Author(s):  
Ewa Sikora ◽  
Anna Bielak-Zmijewska ◽  
Magdalena Dudkowska ◽  
Adam Krzystyniak ◽  
Grazyna Mosieniak ◽  
...  
Keyword(s):  
Glial Cells ◽  
Cellular Senescence ◽  
Dendritic Spines ◽  
Neuronal Plasticity ◽  
Brain Aging ◽  
Aging Brain ◽  
Peripheral Tissues ◽  
Brain Functions ◽  
The Brain

Aging of the brain can manifest itself as a memory and cognitive decline, which has been shown to frequently coincide with changes in the structural plasticity of dendritic spines. Decreased number and maturity of spines in aged animals and humans, together with changes in synaptic transmission, may reflect aberrant neuronal plasticity directly associated with impaired brain functions. In extreme, a neurodegenerative disease, which completely devastates the basic functions of the brain, may develop. While cellular senescence in peripheral tissues has recently been linked to aging and a number of aging-related disorders, its involvement in brain aging is just beginning to be explored. However, accumulated evidence suggests that cell senescence may play a role in the aging of the brain, as it has been documented in other organs. Senescent cells stop dividing and shift their activity to strengthen the secretory function, which leads to the acquisition of the so called senescence-associated secretory phenotype (SASP). Senescent cells have also other characteristics, such as altered morphology and proteostasis, decreased propensity to undergo apoptosis, autophagy impairment, accumulation of lipid droplets, increased activity of senescence-associated-β-galactosidase (SA-β-gal), and epigenetic alterations, including DNA methylation, chromatin remodeling, and histone post-translational modifications that, in consequence, result in altered gene expression. Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons. Interestingly, it has emerged recently, that non-proliferating neuronal cells present in the brain or cultivated in vitro can also have some hallmarks, including SASP, typical for senescent cells that ceased to divide. It has been documented that so called senolytics, which by definition, eliminate senescent cells, can improve cognitive ability in mice models. In this review, we ask questions about the role of senescent brain cells in brain plasticity and cognitive functions impairments and how senolytics can improve them. We will discuss whether neuronal plasticity, defined as morphological and functional changes at the level of neurons and dendritic spines, can be the hallmark of neuronal senescence susceptible to the effects of senolytics.

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