scholarly journals Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 351 ◽  
Author(s):  
Vincenzo Sorrenti ◽  
Sergio Davinelli ◽  
Giovanni Scapagnini ◽  
Bradley J. Willcox ◽  
Richard C. Allsopp ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Brain Aging ◽  
Membrane Surface ◽  
Experimental Models ◽  
Cellular Level ◽  
Human Longevity ◽  
Mitochondrial Functions ◽  
And Function ◽  
The Brain

In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX’s ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector.

scholarly journals Mitochondrial Heterogeneity in the Brain at the Cellular Level

1998 ◽  
Vol 18 (3) ◽  
pp. 231-237 ◽  
Author(s):  
Ursula Sonnewald ◽  
Leif Hertz ◽  
Arne Schousboe
Keyword(s):  
Amino Acid ◽  
Current Knowledge ◽  
Cell Types ◽  
Cellular Level ◽  
Mitochondrial Structure ◽  
Cell Type Specific ◽  
Mitochondrial Heterogeneity ◽  
Specific Tissue ◽  
And Function ◽  
The Brain

Classically, compartmentation of glutamate metabolism in the brain is associated with the fact that neurons and glia exhibit distinct differences with regard to metabolism of this amino acid. The recent use of 13C-labeled compounds to study this metabolism in conjunction with the availability of cell type-specific tissue culture modes has led to the notion that such compartmentation may even be present in individual cell types, neurons as well as glia. To better understand and explain this, it is proposed that mitochondrial heterogeneity may exist resulting in tricarboxylic acid cycles with different properties regarding cycling rates and ratio as well as coupling to amino acid biosynthesis, primarily involving glutamate and aspartate. These hypotheses are evaluated in the light of current knowledge about mitochondrial structure and function.

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 Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors

2020 ◽  
Author(s):  
Shiri Kult ◽  
Tsviya Olender ◽  
Marco Osterwalder ◽  
Sharon Krief ◽  
Ronnie Blecher-Gonen ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Fate ◽  
Single Molecule ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Regulatory Elements ◽  
Transcriptional Enhancer ◽  
Molecular Identity ◽  
And Function

AbstractThe connection between different tissues is vital for the development and function of any organs and systems. In the musculoskeletal system, the attachment of elastic tendons to stiff bones poses a mechanical challenge that is solved by the formation of a transitional tissue, which allows the transfer of muscle forces to the skeleton without tearing. Here, we show that tendon-to-bone attachment cells are bi-fated, activating a mixture of chondrocyte and tenocyte transcriptomes, which is regulated by sharing regulatory elements with these cells and by Krüppel-like factors transcription factors (KLF).To uncover the molecular identity of attachment cells, we first applied high-throughput RNA sequencing to murine humeral attachment cells. The results, which were validated by in situ hybridization and single-molecule in situ hybridization, reveal that attachment cells express hundreds of chondrogenic and tenogenic genes. In search for the underlying mechanism allowing these cells to express these genes, we performed ATAC sequencing and found that attachment cells share a significant fraction of accessible intergenic chromatin areas with either tenocytes or chondrocytes. Epigenomic analysis further revealed transcriptional enhancer signatures for the majority of these regions. We then examined a subset of these regions using transgenic mouse enhancer reporter. Results verified the shared activity of some of these enhancers, supporting the possibility that the transcriptome of attachment cells is regulated by enhancers with shared activities in tenocytes or chondrocytes. Finally, integrative chromatin and motif analyses, as well as the transcriptome data, indicated that KLFs are regulators of attachment cells. Indeed, blocking the expression of Klf2 and Klf4 in the developing limb mesenchyme led to abnormal differentiation of attachment cells, establishing these factors as key regulators of the fate of these cells.In summary, our findings show how the molecular identity of bi-fated attachment cells enables the formation of the unique transitional tissue that connect tendon to bone. More broadly, we show how mixing the transcriptomes of two cell types through shared enhancers and a dedicated set of transcription factors can lead to the formation of a new cell fate that connects them.

Mind Shift

2021 ◽  
Author(s):  
John Parrington
Keyword(s):  
Social Interactions ◽  
Brain Function ◽  
Sense Of Self ◽  
Human Mind ◽  
Cellular Level ◽  
Structure And Function ◽  
Human Consciousness ◽  
The Social ◽  
And Function ◽  
The Brain

This book draws on the latest research on the human brain to show how it differs strikingly from those of other animals in its structure and function at molecular and cellular level. It argues that this ‘shift’, enlarging the brain, giving it greater flexibility and enabling higher functions such as imagination, was driven by tool use, but especially by the development of one remarkable tool—language. The complex social interaction brought by language opened up the possibility of shared conceptual worlds, enriched with rhythmic sounds and images that could be drawn on cave walls. This transformation enabled modern humans to generate an exceptional human consciousness, a sense of self that arises as a product of our brain biology and the social interactions we experience. Linking early work by the Russian psychologist Lev Vygotsky to the findings of modern neuroscience, the book also explores how language, culture, and society mediate brain function, and what this view of the human mind may bring to our understanding and treatment of mental illness.

scholarly journals Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 824
Author(s):  
Andrea Capucciati ◽  
Fabio A. Zucca ◽  
Enrico Monzani ◽  
Luigi Zecca ◽  
Luigi Casella ◽  
...  
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Brain Aging ◽  
Experimental Models ◽  
Test Tube ◽  
Age Related ◽  
And Function ◽  
Endogenous Metabolites ◽  
High Degree

Neuromelanin (NM) accumulates in catecholamine long-lived brain neurons that are lost in neurodegenerative diseases. NM is a complex substance made of melanic, peptide and lipid components. NM formation is a natural protective process since toxic endogenous metabolites are removed during its formation and as it binds excess metals and xenobiotics. However, disturbances of NM synthesis and function could be toxic. Here, we review recent knowledge on NM formation, toxic mechanisms involving NM, go over NM binding substances and suggest experimental models that can help identifying xenobiotic modulators of NM formation or function. Given the high likelihood of a central NM role in age-related human neurodegenerative diseases such as Parkinson’s and Alzheimer’s, resembling such diseases using animal models that do not form NM to a high degree, e.g., mice or rats, may not be optimal. Rather, use of animal models (i.e., sheep and goats) that better resemble human brain aging in terms of NM formation, as well as using human NM forming stem cellbased in vitro (e.g., mid-brain organoids) models can be more suitable. Toxicants could also be identified during chemical synthesis of NM in the test tube.

An overview of sleep medicine

2017 ◽  
Author(s):  
Sudhansu Chokroverty ◽  
Sushanth Bhat
Keyword(s):  
Circadian Rhythms ◽  
Functional Neuroimaging ◽  
Age Groups ◽  
Sleep Medicine ◽  
Cellular Level ◽  
Sleep Architecture ◽  
History Of ◽  
Function Of Sleep ◽  
And Function ◽  
The Brain

The importance of sleep is well recognized today, among both the academic and clinical communities. Advancements and refinement of functional neuroimaging have led to the ability to map various areas of the brain in different stages of sleep, and neurophysiological techniques have allowed researchers to study changes at the cellular level. However, there remain several unanswered fundamental questions about the nature and function of sleep. This chapter provides a brief overview of the history of sleep medicine and the latest theories about the function of sleep. Also discussed are sleep patterns across various age groups, circadian rhythms, sleep architecture, and the glymphatic system as it pertains to sleep.

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 FOXO3, Telomere Dynamics, and Healthy Brain Aging: A COBRE Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 368-368
Author(s):  
Bradley Willcox ◽  
Kamal Masaki ◽  
Richard Allsopp ◽  
Kalpana Kallianpur
Keyword(s):  
Brain Aging ◽  
Peripheral Blood Leukocyte ◽  
Telomerase Activity ◽  
Cellular Aging ◽  
Human Longevity ◽  
Telomere Shortening ◽  
Wide Range ◽  
Brain Structure And Function ◽  
Blood Leukocyte ◽  
And Function

Abstract Human longevity is linked to genetic, cellular, and other complex biological and psychosocial traits. Aging is typically accompanied by gradual brain atrophy and cognitive decline, but the mechanisms are unclear. Cellular aging, characterized by telomere shortening and altered telomerase activity, is related to mortality and brain aging. Decelerated brain aging is associated with greater peripheral blood leukocyte telomere length (LTL) and, we hypothesize, may be linked to FOXO3 genotype. We will use MRI to assess brain structure and function cross-sectionally in 100 Kuakini Honolulu Heart Program Offspring. Atrophy and disrupted functional connectivity, markers of brain aging, will be examined in relation to FOXO3 and LTL. Associations between brain structural and functional differences, FOXO3 genotype and LTL will be investigated over a wide range of ages, controlling for other biological and psychosocial factors. Results may provide insight into mechanisms influencing the rate of brain aging, and may eventually extend human healthspan.

scholarly journals Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function

2008 ◽  
Vol 88 (2) ◽  
pp. 611-638 ◽  
Author(s):  
Richard C. Scarpulla
Keyword(s):  
Transcription Factors ◽  
Mitochondrial Biogenesis ◽  
Target Genes ◽  
Protein Import ◽  
Genetic System ◽  
Environmental Signals ◽  
Mitochondrial Functions ◽  
Promoter Recognition ◽  
Energy Deprivation ◽  
And Function

Mitochondria contain their own genetic system and undergo a unique mode of cytoplasmic inheritance. Each organelle has multiple copies of a covalently closed circular DNA genome (mtDNA). The entire protein coding capacity of mtDNA is devoted to the synthesis of 13 essential subunits of the inner membrane complexes of the respiratory apparatus. Thus the majority of respiratory proteins and all of the other gene products necessary for the myriad mitochondrial functions are derived from nuclear genes. Transcription of mtDNA requires a small number of nucleus-encoded proteins including a single RNA polymerase (POLRMT), auxiliary factors necessary for promoter recognition (TFB1M, TFB2M) and activation (Tfam), and a termination factor (mTERF). This relatively simple system can account for the bidirectional transcription of mtDNA from divergent promoters and key termination events controlling the rRNA/mRNA ratio. Nucleomitochondrial interactions depend on the interplay between transcription factors (NRF-1, NRF-2, PPARα, ERRα, Sp1, and others) and members of the PGC-1 family of regulated coactivators (PGC-1α, PGC-1β, and PRC). The transcription factors target genes that specify the respiratory chain, the mitochondrial transcription, translation and replication machinery, and protein import and assembly apparatus among others. These factors are in turn activated directly or indirectly by PGC-1 family coactivators whose differential expression is controlled by an array of environmental signals including temperature, energy deprivation, and availability of nutrients and growth factors. These transcriptional paradigms provide a basic framework for understanding the integration of mitochondrial biogenesis and function with signaling events that dictate cell- and tissue-specific energetic properties.

scholarly journals A transgenic zebrafish model for the in vivo study of the blood and choroid plexus brain barriers using claudin 5

2017 ◽  
Author(s):  
Lisanne Martine van Leeuwen ◽  
Robert J. Evans ◽  
Kin Ki Jim ◽  
Theo Verboom ◽  
Xiaoming Fang ◽  
...  
Keyword(s):  
Choroid Plexus ◽  
Molecular Transport ◽  
Experimental Models ◽  
Ependymal Cells ◽  
Transgenic Zebrafish ◽  
Zebrafish Model ◽  
Junction Protein ◽  
And Function ◽  
The Brain

ABSTRACTThe central nervous system (CNS) has specific barriers that protect the brain from potential threats and tightly regulate molecular transport. Despite the critical functions of the CNS barriers, the mechanisms underlying their development and function are not well understood, and there are very limited experimental models for their study. Claudin 5 is a tight junction protein required for blood brain barrier (BBB) and choroid plexus (CP) barrier structure and function in humans. Here, we show that the gene claudin 5a is the zebrafish orthologue with high fidelity expression, in the BBB and CP barriers, that demonstrates the conservation of the BBB and CP between humans and zebrafish. Expression of claudin 5a correlates with developmental tightening of the BBB and is restricted to a subset of the brain vasculature clearly delineating the BBB. We show that claudin 5a expressing cells of the CP are ciliated ependymal cells that drive fluid flow in the brain ventricles. Finally, we find that CP development precedes BBB development and that claudin 5a expression occurs simultaneously with angiogenesis. Thus, our novel transgenic zebrafish represents an ideal model to study CNS barrier development and function, critical in understanding the mechanisms underlying CNS barrier function in health and disease.

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