scholarly journals Deciphering the Role of microRNAs in Large-Artery Stiffness Associated With Aging: Focus on miR-181b

2021 ◽  
Vol 12 ◽  
Author(s):  
Jay M. Baraban ◽  
Eric Tuday ◽  
Dan E. Berkowitz ◽  
Sam Das
Keyword(s):  
Focused Attention ◽  
Large Artery ◽  
Arterial Stiffening ◽  
Future Studies ◽  
Innovative Strategies ◽  
Age Dependent ◽  
Artery Stiffness ◽  
Public Health Challenge ◽  
And Function

Large artery stiffness (LAS) is a major, independent risk factor underlying cardiovascular disease that increases with aging. The emergence of microRNA signaling as a key regulator of vascular structure and function has stimulated interest in assessing its role in the pathophysiology of LAS. Identification of several microRNAs that display age-associated changes in expression in aorta has focused attention on defining their molecular targets and deciphering their role in age-associated arterial stiffening. Inactivation of the microRNA-degrading enzyme, translin/trax, which reverses the age-dependent decline in miR-181b, confers protection from aging-associated arterial stiffening, suggesting that inhibitors targeting this enzyme may have translational potential. As LAS poses a major public health challenge, we anticipate that future studies based on these advances will yield innovative strategies to combat aging-associated arterial stiffening.

scholarly journals Understanding the Role of Dysfunctional and Healthy Mitochondria in Stroke Pathology and Its Treatment

2018 ◽  
Vol 19 (7) ◽  
pp. 2127 ◽  
Author(s):  
Hung Nguyen ◽  
Sydney Zarriello ◽  
Mira Rajani ◽  
Julian Tuazon ◽  
Eleonora Napoli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Neurovascular Unit ◽  
The United States ◽  
Stroke Therapy ◽  
Molecular Processes ◽  
Innovative Strategies ◽  
Mitochondria Transfer ◽  
And Function ◽  
Research Endeavor

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cell transplantation, may hold promise as a stroke therapy, because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria—one that is potentially transferrable into ischemic cells—may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells to critically evaluate the potential of mitochondria-based stem cell therapy for stroke patients.

scholarly journals Astrocytes: News about Brain Health and Diseases

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 394
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Glial Cells ◽  
Present State ◽  
Cell Types ◽  
Present Review ◽  
Brain Health ◽  
Traumatic Injuries ◽  
Future Studies ◽  
Brain Physiology ◽  
And Function

Astrocytes, the most numerous glial cells in the brains of humans and other mammalian animals, have been studied since their discovery over 100 years ago. For many decades, however, astrocytes were believed to operate as a glue, providing only mechanical and metabolic support to adjacent neurons. Starting from a “revolution” initiated about 25 years ago, numerous astrocyte functions have been reconsidered, some previously unknown, others attributed to neurons or other cell types. The knowledge of astrocytes has been continuously growing during the last few years. Based on these considerations, in the present review, different from single or general overviews, focused on six astrocyte functions, chosen due in their relevance in both brain physiology and pathology. Astrocytes, previously believed to be homogeneous, are now recognized to be heterogeneous, composed by types distinct in structure, distribution, and function; their cooperation with microglia is known to govern local neuroinflammation and brain restoration upon traumatic injuries; and astrocyte senescence is relevant for the development of both health and diseases. Knowledge regarding the role of astrocytes in tauopathies and Alzheimer’s disease has grow considerably. The multiple properties emphasized here, relevant for the present state of astrocytes, will be further developed by ongoing and future studies.

scholarly journals The Phosphoglycerate Kinase (PGK) Gene Family of Maize (Zea mays var. B73)

Plants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1639
Author(s):  
Julio A. Massange-Sánchez ◽  
Luz E. Casados-Vázquez ◽  
Sheila Juarez-Colunga ◽  
Ruairidh J. H. Sawers ◽  
Axel Tiessen
Keyword(s):  
Phylogenetic Analysis ◽  
Zea Mays ◽  
Leaf Blade ◽  
Phosphoglycerate Kinase ◽  
Future Studies ◽  
Plant Genomes ◽  
Key Enzyme ◽  
And Function ◽  
Distinct Role

Phosphoglycerate kinase (PGK, E.C. 2.7.2.3) interconverts ADP + 1,3-bisphospho-glycerate (1,3-bPGA) to ATP + 3-phosphoglycerate (3PGA). While most bacteria have a single pgk gene and mammals possess two copies, plant genomes contain three or more PGK genes. In this study, we identified five Pgk genes in the Zea mays var. B73 genome, predicted to encode proteins targeted to different subcellular compartments: ZmPgk1, ZmPgk2, and ZmPgk4 (chloroplast), ZmPgk3 (cytosol), and ZmPgk5 (nucleus). The expression of ZmPgk3 was highest in non-photosynthetic tissues (roots and cobs), where PGK activity was also greatest, consistent with a function in glycolysis. Green tissues (leaf blade and husk leaf) showed intermediate levels of PGK activity, and predominantly expressed ZmPgk1 and ZmPgk2, suggesting involvement in photosynthetic metabolism. ZmPgk5 was weakly expressed and ZmPgk4 was not detected in any tissue. Phylogenetic analysis showed that the photosynthetic and glycolytic isozymes of plants clustered together, but were distinct from PGKs of animals, fungi, protozoa, and bacteria, indicating that photosynthetic and glycolytic isozymes of plants diversified after the divergence of the plant lineage from other groups. These results show the distinct role of each PGK in maize and provide the basis for future studies into the regulation and function of this key enzyme.

scholarly journals Immunosenescence in Choroidal Neovascularization (CNV)—Transcriptional Profiling of Naïve and CNV-Associated Retinal Myeloid Cells during Aging

2021 ◽  
Vol 22 (24) ◽  
pp. 13318
Author(s):  
Anja Schlecht ◽  
Adrian Thien ◽  
Julian Wolf ◽  
Gabriele Prinz ◽  
Hansjürgen Agostini ◽  
...  
Keyword(s):  
Choroidal Neovascularization ◽  
Transcriptional Profiling ◽  
Myeloid Cells ◽  
Age Related Macular Degeneration ◽  
Physiological Aging ◽  
Future Studies ◽  
Signature Genes ◽  
Age Related ◽  
Age Dependent

Immunosenescence is considered a possible factor in the development of age-related macular degeneration and choroidal neovascularization (CNV). However, age-related changes of myeloid cells (MCs), such as microglia and macrophages, in the healthy retina or during CNV formation are ill-defined. In this study, Cx3cr1-positive MCs were isolated by fluorescence-activated cell sorting from six-week (young) and two-year-old (old) Cx3cr1GFP/+ mice, both during physiological aging and laser-induced CNV development. High-throughput RNA-sequencing was performed to define the age-dependent transcriptional differences in MCs during physiological aging and CNV development, complemented by immunohistochemical characterization and the quantification of MCs, as well as CNV size measurements. These analyses revealed that myeloid cells change their transcriptional profile during both aging and CNV development. In the steady state, senescent MCs demonstrated an upregulation of factors contributing to cell proliferation and chemotaxis, such as Cxcl13 and Cxcl14, as well as the downregulation of microglial signature genes. During CNV formation, aged myeloid cells revealed a significant upregulation of angiogenic factors such as Arg1 and Lrg1 concomitant with significantly enlarged CNV and an increased accumulation of MCs in aged mice in comparison to young mice. Future studies need to clarify whether this observation is an epiphenomenon or a causal relationship to determine the role of immunosenescence in CNV formation.

scholarly journals Function, Role, and Clinical Application of MicroRNAs in Vascular Aging

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao Lin ◽  
Jun-Kun Zhan ◽  
Yan-Jiao Wang ◽  
Pan Tan ◽  
Yi-Yin Chen ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cell Biology ◽  
Atherosclerotic Plaques ◽  
Messenger Rnas ◽  
Vascular Aging ◽  
Small Noncoding Rnas ◽  
Age Dependent ◽  
And Function ◽  
Threshold Process

Vascular aging, a specific type of organic aging, is related to age-dependent changes in the vasculature, including atherosclerotic plaques, arterial stiffness, fibrosis, and increased intimal thickening. Vascular aging could influence the threshold, process, and severity of various cardiovascular diseases, thus making it one of the most important risk factors in the high mortality of cardiovascular diseases. As endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are the main cell biological basis of these pathology changes of the vasculature, the structure and function of ECs and VSMCs play a key role in vascular aging. MicroRNAs (miRNAs), small noncoding RNAs, have been shown to regulate the expression of multiple messenger RNAs (mRNAs) posttranscriptionally, contributing to many crucial aspects of cell biology. Recently, miRNAs with functions associated with aging or aging-related diseases have been studied. In this review, we will summarize the reported role of miRNAs in the process of vascular aging with special emphasis on EC and VSMC functions. In addition, the potential application of miRNAs to clinical practice for the diagnosis and treatment of cardiovascular diseases will also be discussed.

scholarly journals Central Fat Mass Versus Peripheral Fat and Lean Mass: Opposite (Adverse Versus Favorable) Associations with Arterial Stiffness? The Amsterdam Growth and Health Longitudinal Study

2004 ◽  
Vol 89 (6) ◽  
pp. 2632-2639 ◽  
Author(s):  
Isabel Ferreira ◽  
Marieke B. Snijder ◽  
Jos W. R. Twisk ◽  
Willem van Mechelen ◽  
Han C. G. Kemper ◽  
...  
Keyword(s):  
Body Composition ◽  
Lean Mass ◽  
The Other ◽  
Large Artery ◽  
Protective Effects ◽  
Degree Of Protection ◽  
Artery Stiffness ◽  
Central Fat ◽  
The One

Abstract Central and peripheral fatness seem to confer opposite (i.e. adverse vs. protective) effects on cardiovascular risk, but how this occurs is not clear. In addition, the role of peripheral lean mass needs to be elucidated. We therefore investigated, in 336 (175 women) 36-yr-old and apparently healthy adults, the relationship between trunk fat, peripheral fat, and peripheral lean mass on the one hand, and estimates of stiffness of three large arteries on the other. Body composition was assessed by dual-energy x-ray absorptiometry. Arterial properties were assessed by ultrasound imaging. We found that 1) trunk fat was positively (i.e. adversely) associated with stiffness of the carotid and femoral arteries, whereas peripheral fat was inversely (i.e. favorably) associated with stiffness of the brachial and the carotido-femoral segment; 2) peripheral lean mass was positively associated with arterial diameter and carotid compliance and inversely associated with stiffness of the carotido-femoral segment; and 3) after adjustment for the other body composition variables, the above-mentioned associations remained, but peripheral fat in addition became, if anything, favorably associated with stiffness of the femoral artery. We conclude that trunk fat is adversely associated with large artery stiffness, whereas some degree of protection is conferred by peripheral fat and lean mass.

scholarly journals A LRRK2/dLRRK-mediated lysosomal pathway that contributes to glial cell death and DA neuron survival

2021 ◽  
Author(s):  
Linfang Wang ◽  
Honglei Wang ◽  
Margaret S Ho
Keyword(s):  
Caspase 3 ◽  
Kinase Activity ◽  
Dependent Manner ◽  
Dopaminergic Neurodegeneration ◽  
Age Dependent ◽  
Sporadic Parkinson’S Disease ◽  
Locomotor Deficits ◽  
And Function ◽  
Reduced Activity

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial and sporadic Parkinson's disease (PD). A plethora of evidence has indicated a role for LRRK2 in endolysosomal trafficking in neurons, while LRRK2 function in glia, although highly expressed, remains largely unknown. Here we present evidence that LRRK2/dLRRK mediates a glial lysosomal pathway that contributes to the mechanism of PD. Independent of its kinase activity, glial LRRK2/dLRRK knockdown in the immortalized microglial cells or flies results in enlarged and swelling lysosomes fewer in number. These lysosomes are less mobile, wrongly acidified, and exhibit defective membrane permeability and reduced activity of the lysosome hydrolase cathespin B. In addition, microglial LRRK2 depletion causes increased Caspase 3 levels, leading to glial apoptosis, dopaminergic neurodegeneration, and locomotor deficits in an age-dependent manner. Taken together, these findings demonstrate a functional role of LRRK2/dLRRK in regulating the glial lysosomal pathway; deficits in lysosomal biogenesis and function linking to glial apoptosis potentially underlie the mechanism of DA neurodegeneration, contributing to the progression of PD.

scholarly journals UNDERSTANDING THE ROLE OF DYSFUNCTIONAL AND HEALTHY MITOCHONDRIA IN STROKE PATHOLOGY AND ITS TREATMENT

2018 ◽  
Author(s):  
Hung Nguyen ◽  
Sydney Zarriello ◽  
Mira Rajani ◽  
Julian Tuazon ◽  
Eleonora Napoli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neurovascular Unit ◽  
The United States ◽  
Stroke Therapy ◽  
Innovative Strategies ◽  
Mitochondria Transfer ◽  
Stem Cells Transplantation ◽  
And Function ◽  
Research Endeavor

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

scholarly journals Implications of NAD+ Metabolism in the Aging Retina and Retinal Degeneration

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Ravirajsinh N. Jadeja ◽  
Menaka C. Thounaojam ◽  
Manuela Bartoli ◽  
Pamela M. Martin
Keyword(s):  
Nad Metabolism ◽  
Age Related ◽  
Promising Therapeutic Target ◽  
Organ Systems ◽  
Age Dependent ◽  
The Subject ◽  
Mitochondrial Oxidative Damage ◽  
And Function ◽  
Visual Health

Nicotinamide adenine dinucleotide (NAD+) plays an important role in various key biological processes including energy metabolism, DNA repair, and gene expression. Accumulating clinical and experimental evidence highlights an age-dependent decline in NAD+ levels and its association with the development and progression of several age-related diseases. This supports the establishment of NAD+ as a critical regulator of aging and longevity and, relatedly, a promising therapeutic target to counter adverse events associated with the normal process of aging and/or the development and progression of age-related disease. Relative to the above, the metabolism of NAD+ has been the subject of numerous investigations in various cells, tissues, and organ systems; however, interestingly, studies of NAD+ metabolism in the retina and its relevance to the regulation of visual health and function are comparatively few. This is surprising given the critical causative impact of mitochondrial oxidative damage and bioenergetic crises on the development and progression of degenerative disease of the retina. Hence, the role of NAD+ in this tissue, normally and aging and/or disease, should not be ignored. Herein, we discuss important findings in the field of NAD+ metabolism, with particular emphasis on the importance of the NAD+ biosynthesizing enzyme NAMPT, the related metabolism of NAD+ in the retina, and the consequences of NAMPT and NAD+ deficiency or depletion in this tissue in aging and disease. We discuss also the implications of potential therapeutic strategies that augment NAD+ levels on the preservation of retinal health and function in the above conditions. The overarching goal of this review is to emphasize the importance of NAD+ metabolism in normal, aging, and/or diseased retina and, by so doing, highlight the necessity of additional clinical studies dedicated to evaluating the therapeutic utility of strategies that enhance NAD+ levels in improving vision.

scholarly journals Retromer subunit, VPS29, regulates synaptic transmission and is required for endolysosomal function in the aging brain

2019 ◽  
Author(s):  
Hui Ye ◽  
Shamsideen Ojelade ◽  
David Li-Kroeger ◽  
Zhongyuan Zuo ◽  
Liping Wang ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Adult Brain ◽  
Aging Brain ◽  
Gtpase Activating Protein ◽  
Ultrastructural Evidence ◽  
Age Dependent ◽  
Aging Adults ◽  
And Function ◽  
Brain Homeostasis

AbstractRetromer, including Vps35, Vps26, and Vps29, is a protein complex responsible for recycling proteins within the endolysosomal pathway. Although implicated in both Parkinson’s and Alzheimer’s disease, our understanding of retromer function in the adult brain remains limited, in part because Vps35 and Vps26 are essential for development. In Drosophila, we find that Vps29 is dispensable for embryogenesis but required for retromer function in aging adults, including for synaptic transmission, survival, and locomotion. Unexpectedly, in Vps29 mutants, Vps35 and Vps26 proteins are normally expressed and associated, but retromer is mislocalized from neuropil to soma with the Rab7 GTPase. Further, Vps29 phenotypes are suppressed by reducing Rab7 or overexpressing the GTPase activating protein, TBC1D5. With aging, retromer insufficiency triggers progressive endolysosomal dysfunction, with ultrastructural evidence of impaired substrate clearance and lysosomal stress. Our results reveal the role of Vps29 in retromer localization and function, highlighting requirements for brain homeostasis in aging.Impact StatementVps29 promotes retromer localization in the adult Drosophila brain, engaging Rab7 and TBC1D5, and its loss triggers age-dependent neuronal impairments in endolysosomal trafficking and synaptic transmission.

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