The Interplay between Mitochondrial Morphology and Myomitokines in Aging Sarcopenia

Sarcopenia is a chronic disease characterized by the progressive loss of skeletal muscle mass, force, and function during aging. It is an emerging public problem associated with poor quality of life, disability, frailty, and high mortality. A decline in mitochondria quality control pathways constitutes a major mechanism driving aging sarcopenia, causing abnormal organelle accumulation over a lifetime. The resulting mitochondrial dysfunction in sarcopenic muscles feedbacks systemically by releasing the myomitokines fibroblast growth factor 21 (FGF21) and growth and differentiation factor 15 (GDF15), influencing the whole-body homeostasis and dictating healthy or unhealthy aging. This review describes the principal pathways controlling mitochondrial quality, many of which are potential therapeutic targets against muscle aging, and the connection between mitochondrial dysfunction and the myomitokines FGF21 and GDF15 in the pathogenesis of aging sarcopenia.

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Quercetin ameliorates mitochondrial dysfunction and mitigates methamphetamine-induced anxiety-like behavior

10.1101/2021.06.29.450268 ◽

2021 ◽

Author(s):

Fengrong Chen ◽

Jiaxue Sun ◽

Yongjin Zhang ◽

Yicong Dai ◽

Zherui Zhang ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Oxygen Consumption ◽

Mitochondrial Dysfunction ◽

Consumption Rate ◽

Mitochondrial Morphology ◽

Transmission Electron ◽

Anxiety Behavior ◽

And Function

Methamphetamine (MA) abuse results in neurotoxic outcomes, including increased anxiety and depression, during both MA use and withdrawal. Although numerous studies have reported an association between MA exposure and anxiety, the underlying mechanism remains elusive. In this study, escalating dose of MA was used to establish an MA-treated mouse model presenting anxiety behavior. RNA seq was then performed to profile the gene expression patterns in the hippocampus (HIPP). Differentially expressed genes (DEGs) were identified and function enrichment analysis was conducted to explore the underlying mechanisms. Quercetin as an mitochondria protector was used in vivo and in vitro. The C57BL/6J mice were co-treated with 50 mg/kg Quercetin and escalating MA. Anxiety behavior was evaluated by utilizing the elevated plus maze and the open field test. Transmission electron microscopy and immunohistochemistry were conducted to study the pathology of MA-inducced anxiety . The effects of MA and Quercetin on astrocytes were investigated by fluorescence staining, transmission electron microscopy, flow cytometry, and oxygen consumption rate. Western blot and qPCR were performed to analyze altered protein and gene levels of HIPP in mice and astrtocytes. The results demonstrated that forteen upregulated differentially expressed genes were identified and significantly enriched in signaling pathways related to psychiatric disorders and mitochondrial function. Interestingly, we found that quercetin was able to alleviate MA-induced anxiety-like behavior by improving neuron number and mitochondria injury. Mechanistically, quercetin can mitigate aberrant mitochondrial morphology and mitochondrial dysfunction not only by decreasing the levels of total cytoplasmic reactive oxygen species (ROS), mitochondria-derived ROS (mtROS), and mitochondrial membrane potential (MMP), but also increasing the oxygen consumption rate (OCR) and mitochondrial ATP production in vitro, indicating Quercetin ameliorated MA-induced anxiety-like behavior by modifying mitochondrial morphology and function. Furthermore, quercetin reversed OPA1 and DRP1 expression in astrocytes, and mitigated astrocyte activation and the release of inflammatory factors, which can trigger neuronal apoptosis and synaptic loss. Taken together, we provided evidence showing that MA can induce anxiety-like behavior via the induction of oxidative stress and mitochondrial dysfunction. Quercetin exerted antipsychotic activity through mitochondrial modulation, suggesting its potential for further therapeutic development in MA-induced anxiety.

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DROSOPHILA MTOR COMPLEX 2 PRESERVES MITOCHONDRIAL AND CARDIAC FUNCTION UNDER HIGH FAT DIET TREATMENT

10.1101/2021.01.27.428443 ◽

2021 ◽

Author(s):

Kai Chang ◽

Guillermo A. Requejo Figueroa ◽

Hua Bai

Keyword(s):

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Mitochondrial Morphology ◽

Contractile Dysfunction ◽

Wild Type ◽

High Fat ◽

Mitochondrial Homeostasis ◽

Mechanistic Target Of Rapamycin ◽

And Function ◽

Mtor Complex 1

AbstractHigh fat diet (HFD)-associated lipotoxicity is one of the major causes of cardiovascular diseases. The mechanistic target of rapamycin (mTOR) pathway, especially mTOR complex 1 (mTORC1), has been previously implicated in HFD-induced heart dysfunction. In the present study, we find that unlike mTORC1, mTOR complex 2 (mTORC2) protects hearts from HFD-induced cardiomyopathy and mitochondrial dysfunction in Drosophila. We show that HFD feeding induces contractile dysfunction along with altered mitochondrial morphology and function. Upon HFD feeding, the mitochondria of cardiomyocytes exhibit fragmentation, loss of membrane potential, and calcium overload. Interestingly, HFD feeding also reduces the activity of cardiac mTORC2. In line with this finding, the flies with cardiac-specific knockdown of rictor, the key subunit of mTORC2, show cardiac and mitochondrial dysfunction similar to what is observed in HFD-fed wild-type flies. Conversely, cardiac-specific activation of mTORC2 by overexpressing rictor attenuates HFD-induced mitochondrial and cardiac dysfunction. Thus, our findings suggest that mTORC2 is a cardioprotective factor and regulates mitochondrial homeostasis upon HFD feeding.

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Mitochondrial functionality in female reproduction

Postępy Higieny i Medycyny Doświadczalnej ◽

10.5604/01.3001.0010.3848 ◽

2017 ◽

Vol 71 (1) ◽

pp. 0-0

Author(s):

Łukasz Gąsior ◽

Regina Daszkiewicz ◽

Mateusz Ogórek ◽

Zbigniew Polański

Keyword(s):

Mitochondrial Genome ◽

Germ Cells ◽

Germ Line ◽

Whole Body ◽

Female Reproduction ◽

Normal Number ◽

Female Germ Line ◽

And Function ◽

Role And Function

In most animal species female germ cells are the source of mitochondrial genome for the whole body of individuals. As a source of mitochondrial DNA for future generations the mitochondria in the female germ line undergo dynamic quantitative and qualitative changes. In addition to maintaining the intact template of mitochondrial genome from one generation to another, mitochondrial role in oocytes is much more complex and pleiotropic. The quality of mitochondria determines the ability of meiotic divisions, fertilization ability, and activation after fertilization or sustaining development of a new embryo. The presence of normal number of functional mitochondria is also crucial for proper implantation and pregnancy maintaining. This article addresses issues of mitochondrial role and function in mammalian oocyte and presents new approaches in studies of mitochondrial function in female germ cells.

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Case Report on a Misdiagnosed Case of Subcortical Vascular Dementia – the Importance of Sound Knowledge of Psychiatry With Proper History Taking

Archives of Psychiatry Research ◽

10.20471/dec.2021.57.02.09 ◽

2021 ◽

Vol 57 (2) ◽

pp. 199-210

Author(s):

Natasha Subhas ◽

Nicholas Tze Ping Pang ◽

Kok Yoon Chee ◽

Norzaini Rose Mohd Zain ◽

Kok Liang Teng ◽

...

Keyword(s):

Vascular Dementia ◽

Psychiatric Symptoms ◽

Quality Of Healthcare ◽

Poor Quality ◽

Brain Scans ◽

Subcortical Vascular Dementia ◽

Assessment And Treatment ◽

Post Stroke Depression ◽

And Function

Psychiatric symptoms at presentation may often be missed, if not suspected or specifically explored. A missed psychiatric diagnosis may lead to dire consequences in terms of poor quality of life and function for the patient, affecting overall quality of healthcare provided. This lady presented with depressive symptoms after multiple strokes and was initially diagnosed as post stroke depression. However, after it was observed that she did not show any improvement in symptoms despite being on antidepressants, subsequent further investigations revealed a history more suggestive of subcortical vascular dementia. Consequently, detailed neuropsychological and neuropsychiatric assessments, including NUCOG, and relevant investigations including MRI brain scans were performed suggesting a diagnosis of vascular dementia. This case illustrates that an insufficiently thorough assessment and treatment process results in unnecessary morbidity, prolongs duration of illness, and increases social and occupational dysfunction to the patient. Hence, it further underscores the need to perform a thorough history, physical examination and relevant investigations to ensure organic etiologies are ruled out in clients with relevant sociodemographic and clinical risk factors.

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Molecular Basis for the Therapeutic Effects of Exercise on Mitochondrial Defects

Frontiers in Physiology ◽

10.3389/fphys.2020.615038 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jonathan M. Memme ◽

David A. Hood

Keyword(s):

Skeletal Muscle ◽

Mitochondrial Dysfunction ◽

Muscle Pathology ◽

Therapeutic Effects ◽

Atp Production ◽

Muscle Aging ◽

Mitochondrial Defects ◽

Aging Muscle ◽

Skeletal Muscle Aging ◽

And Function

Mitochondrial dysfunction is common to many organ system disorders, including skeletal muscle. Aging muscle and diseases of muscle are often accompanied by defective mitochondrial ATP production. This manuscript will focus on the pre-clinical evidence supporting the use of regular exercise to improve defective mitochondrial metabolism and function in skeletal muscle, through the stimulation of mitochondrial turnover. Examples from aging muscle, muscle-specific mutations and cancer cachexia will be discussed. We will also examine the effects of exercise on the important mitochondrial regulators PGC-1α, and Parkin, and summarize the effects of exercise to reverse mitochondrial dysfunction (e.g., ROS production, apoptotic susceptibility, cardiolipin synthesis) in muscle pathology. This paper will illustrate the breadth and benefits of exercise to serve as “mitochondrial medicine” with age and disease.

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Strategi Politik-Hukum Meningkatkan Kualitas Kinerja DPR Ri Dalam Produktivitas Legislasi Nasional

JURNAL CITA HUKUM ◽

10.15408/jch.v4i2.4140 ◽

2016 ◽

Vol 4 (2) ◽

Author(s):

Agus Riswanto

Keyword(s):

Public Participation ◽

House Of Representatives ◽

Secondary Data ◽

Poor Quality ◽

Legal Research ◽

And Function ◽

Role And Function ◽

Member Of Parliament ◽

Research Analysis

ABSTRACT: This study examines and learn more on the need to improve the functioning of the House of Representatives (DPR RI) in national legislation. The main problem of the functions of Parliament in every period of the membership of Parliament from 2005-2016 year is the low productivity performance of the Parliament in legislation. This research is a normative law (legal research) or doctrinal explorative research-analysis. The data used is secondary data, in the form of material and the primary law and secondary law. The results showed the main causes of poor quality of legislation the DPR RI because of the extreme multiparty, Parliament favored the performance of supervisory functions in the executive and member of Parliament in the discipline in the use of his time. The legal policy strategy to improve the productivity of legislation DPR RI is, change the course of politics from the agent/delegete to the trustee, eliminating the function of the fraction DPR RI, balancing the role and function of DPR RI and DPD RI, accommodate veto the president, increasing public participation, and streamline costs in making law. ABSTRAK Penelitian ini mengkaji dan mendalami tentang perlunya DPR RI meningkatkan fungsi legislasi nasional. Problem utama fungsi DPR dalam setiap periode keanggotaan DPR dari tahun 2005-2016 adalah rendahnya kinerja DPR dalam produktivitas legislasi. Penelitian ini merupakan penelitian hukum normatif (legal research) atau penelitian doktrinal yang bersifat eksploratif-analisis. Data yang digunakan adalah data sekunder, berupa bahan hukum primer dan dan bahan hukum sekunder. Hasil penelitian menunjukan penyebab utama rendahnya kualitas produk legislasi DPR karena faktor multipartai ekstrim, DPR lebih mengutamakan pada fungsi kinerja pengawasan pada eksekutif dan rendahnya disiplin anggota DPR dalam memanfaatkan waktunya. Adapun strategi politik-hukum untuk meningkatkan kualitas produktifitas legislasi DPR adalah, mengubah haluan politik dari agent/delegete ke trustee, menghilangkan fungsi fraksi di DPR RI, menyeimbangkan peran dan fungsi DPR RI dengan DPD RI, mengakomodasi hak veto pada presiden, meningkatkan partisipasi publik, dan mengefektifkan biaya dalam pembuatan undang-undang. DOI: 10.15408/jch.v4i2.4140

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Sarcopenia, Currently a Hot Topic: A Narrative Review

The Asian Journal of Kinesiology ◽

10.15758/ajk.2021.23.1.20 ◽

2021 ◽

Vol 23 (1) ◽

pp. 20-26

Author(s):

JungHoon Chai ◽

HyunJoo Kang

Keyword(s):

Skeletal Muscle ◽

Poor Quality ◽

Adverse Outcomes ◽

Narrative Review ◽

Amino Acid Supplementation ◽

Muscle Loss ◽

Progressive Decline ◽

Life And Death ◽

And Function

Aging is associated with a progressive decline of skeletal muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and a condition known as sarcopenia. Sarcopenia is a syndrome a risk of adverse outcomes such as physical disability, poor quality of life and death. Agerelated losses in skeletal muscle mass and function have had a significant important in health care issue. In this study, we reviewed the recently introduced criteria for the Eastern and Western diagnosis of sarcopenia. A narrative review of evidence- and non-evidence-based papers was conducted, using a relevant methodological framework. This review is included the following: 1) definitions and diagnostic criteria over time; 2) pathophysiology of muscle loss; 3) management especially protein or amino acid supplementation, medications, and physical exercise.

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Mandibular reconstruction: a review

Update Dental College Journal ◽

10.3329/updcj.v9i2.43742 ◽

2019 ◽

Vol 9 (2) ◽

pp. 50-54

Author(s):

Mir Nowazesh Ali ◽

Rezwana Binte Anwar ◽

Ruman Banik ◽

Sajid Hasan ◽

Md Raihan Ul Arefin ◽

...

Keyword(s):

Quality Of Life ◽

Inferior Alveolar Nerve ◽

Malignant Tumour ◽

Poor Quality ◽

Mandibular Reconstruction ◽

Facial Disfigurement ◽

Form And Function ◽

And Function ◽

Improve Patient

Mandibular defects may occur from maxillofacial injury, inflammatory disease, benign or malignant tumour resections and osteoradionecrosis. Mastication, speech and facial disfigurement are often severely compromised without reconstruction leading to poor quality of life. The goal of mandibular reconstruction is to restore facial form and function, repair of mandibular continuity and soft tissue reanimation. Implant insertion should be feasible to allow occlusal rehabilitation and if possible the inferior alveolar nerve function should be restored. Mandibular reconstruction principles and techniques have evolved dramatically over the years. Refinements in techniques continue to improve patient quality of life. This paper reviews short history, current techniques and few promising future endevours related to mandibular reconstruction. Update Dent. Coll. j: 2019; 9 (2): 50-54

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Adrenergic Regulation of Drp1-Driven Mitochondrial Fission in Cardiac Physio-Pathology

Antioxidants ◽

10.3390/antiox7120195 ◽

2018 ◽

Vol 7 (12) ◽

pp. 195 ◽

Cited By ~ 14

Author(s):

Bong Jhun ◽

Jin O-Uchi ◽

Stephanie Adaniya ◽

Michael Cypress ◽

Yisang Yoon

Keyword(s):

Mitochondrial Dysfunction ◽

Molecular Mechanisms ◽

Mitochondrial Fission ◽

Ros Generation ◽

Mitochondrial Morphology ◽

Mitochondrial Fragmentation ◽

Cellular Functions ◽

Post Translational Modifications ◽

Signaling Activation ◽

And Function

Abnormal mitochondrial morphology, especially fragmented mitochondria, and mitochondrial dysfunction are hallmarks of a variety of human diseases including heart failure (HF). Although emerging evidence suggests a link between mitochondrial fragmentation and cardiac dysfunction, it is still not well described which cardiac signaling pathway regulates mitochondrial morphology and function under pathophysiological conditions such as HF. Mitochondria change their shape and location via the activity of mitochondrial fission and fusion proteins. This mechanism is suggested as an important modulator for mitochondrial and cellular functions including bioenergetics, reactive oxygen species (ROS) generation, spatiotemporal dynamics of Ca2+ signaling, cell growth, and death in the mammalian cell- and tissue-specific manners. Recent reports show that a mitochondrial fission protein, dynamin-like/related protein 1 (DLP1/Drp1), is post-translationally modified via cell signaling pathways, which control its subcellular localization, stability, and activity in cardiomyocytes/heart. In this review, we summarize the possible molecular mechanisms for causing post-translational modifications (PTMs) of DLP1/Drp1 in cardiomyocytes, and further discuss how these PTMs of DLP1/Drp1 mediate abnormal mitochondrial morphology and mitochondrial dysfunction under adrenergic signaling activation that contributes to the development and progression of HF.

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PINK1 Activation Attenuates Impaired Neuronal-Like Differentiation and Synaptogenesis and Mitochondrial Dysfunction in Alzheimer’s Disease Trans-Mitochondrial Cybrid Cells

Journal of Alzheimer s Disease ◽

10.3233/jad-210095 ◽

2021 ◽

pp. 1-13

Author(s):

Fang Du ◽

Qing Yu ◽

Shirley ShiDu Yan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mitochondrial Dysfunction ◽

Energy Homeostasis ◽

Early Stage ◽

Mitochondrial Morphology ◽

Mitochondrial Functions ◽

Lentivirus Transduction ◽

And Function ◽

Human Brains

Background: Mitochondrial dysfunction, bioenergetic deficit, and extensive oxidative stress underlie neuronal perturbation during the early stage of Alzheimer’s disease (AD). Previously, we demonstrated that decreased PTEN-induced putative kinase 1 (PINK1) expression is associated with AD pathology in AD-affected human brains and AD mice. Objective: In the present study, we highlight the essential role of PINK1 in AD-relevant mitochondrial perturbation and neuronal malfunction. Methods: Using trans-mitochondrial “cybrid” (cytoplasmic hybrid) neuronal cells, whose mitochondria are transferred from platelets of patients with sporadic AD, we observed the effect of PINK1 in neuronal-like differentiation and synaptogenesis and mitochondrial functions. Results: In AD cybrid cells, the downregulation of PINK1 is correlated to the alterations in mitochondrial morphology and function and deficit in neuronal-like differentiation. Restoring/increasing PINK1 by lentivirus transduction of PINK1 robustly attenuate mitochondrial defects and rescue neurite-like outgrowth. Importantly, defective PINK1 kinase activity fails to reverse these detrimental effects. Mechanistically, AD cybrid cells reveal a significant decrease in PINK1-dependent phosphorylated mitofusin (Mfn) 2, a key mitochondrial membrane protein that participates in mitochondrial fusion, and an insufficient autophagic activity for clearance of dysfunctional mitochondria. Overexpression of PINK1, but not mutant PINK1 elevates phosphorylation of Mfn2 and autophagy signaling LC3-II. Accordingly, PINK1-overexpressed AD cybrids exhibit increases in mitochondrial length and density and suppressed reactive oxygen species. These results imply that activation of PINK1 protects against AD-affected mitochondrial dysfunction and impairment in neuronal maturation and differentiation. Conclusion: PINK1-mediated mitophagy is important for maintaining mitochondrial health by clearance of dysfunctional mitochondria and therefore, improves energy homeostasis in AD.

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