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Journal of Orthopaedic Translation Jul 2022Sarcopenia is a hallmark of the ageing process, which is characterized by the decline in muscle mass and strength. Growing evidence indicates that mitochondria... (Review)
Review
BACKGROUND
Sarcopenia is a hallmark of the ageing process, which is characterized by the decline in muscle mass and strength. Growing evidence indicates that mitochondria dysfunction play core roles in this process. Meanwhile, physical exercise is regarded as one of the efficiency therapies to attenuate sarcopenia via regulating mitochondrial function during ageing. However, the specific mechanisms among exercise, mitochondrial function and sarcopenia are still unclear. The aim of this systematic review is to delineate the effects of physical exercise on mitochondria during ageing in order to explore potential target for rescuing sarcopenia.
METHODS
A systematic literature search was performed in PubMed, Embase and Web of Science. Information was extracted from the included studies for review.
RESULTS
In this review, 16 pre-clinical studies were included and 105 clinical studies that were not mechanistic research were excluded. 16 pre-clinical studies provided evidence that physical exercise could affect mitochondrial quality control to attenuate sarcopenia. Most of the included studies described the important role of mitochondrial dynamic equilibrium in sarcopenia and showed that effective physical exercise could influence mitochondrial biogenesis, fusion, fission and mitophagy to attenuate sarcopenia in aged animal.
CONCLUSIONS
This systematic review provides an up-to-date sequential overview and highlights the link in the potential mitochondria-related target and physical exercise in aged animal.
TRANSLATION OF THIS ARTICLE
Currently, there is no standard treatment method for sarcopenia. This systematic review revealed the underlying mechanisms for how physical exercise improved muscle performance via regulating mitochondrial dynamic equilibrium, which could provide scientific support for using exercise as a timely intervention for sarcopenia. Additionally, this systematic review allows a better understanding of mitochondrial dynamic equilibrium and exercise for future development of new therapeutic interventions to attenuate sarcopenia.
PubMed: 36090001
DOI: 10.1016/j.jot.2022.06.003 -
Nutrients Aug 2022The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a... (Review)
Review
UNLABELLED
The therapeutic effects of food rich in ellagitannins have been established to stem from its microbial metabolite, urolithin. Over the past decade, there has been a growing trend in urolithin research pertaining to its pharmacological properties. The purpose of this systematic review is to collate and synthesise all available data on urolithin's therapeutic ability, to highlight its potential as a pharmaceutical agent, and prospective direction on future research.
METHODS
This systematic review was written based on the PRISMA guideline and was conducted across Ovid via Embase, Ovid MEDLINE, Cochrane Central Register for Controlled Trials, and Web of Science Core Collection.
RESULTS
A total of 41 animal studies were included in this systematic review based on the appropriate keyword. The included studies highlighted the neuroprotective, anti-metabolic disorder activity, nephroprotective, myocardial protective, anti-inflammatory, and musculoskeletal protection of urolithin A, B, and its synthetic analogue methylated urolithin A. The Sirt1, AMPK, and PI3K/AKT/mTOR signalling pathways were reported to be involved in the initiation of autophagy and mitochondrial biogenesis by urolithin A.
CONCLUSIONS
This review methodically discusses the therapeutic prospects of urolithins and provides scientific justification for the potential development of urolithin A as a potent natural mitophagy inducer for anti-ageing purposes.
Topics: Animals; Coumarins; Hydrolyzable Tannins; Phosphatidylinositol 3-Kinases; Prospective Studies
PubMed: 36079752
DOI: 10.3390/nu14173494 -
Cells Aug 2022Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease (DKD). Compared to the vast body of evidence from preclinical in vitro and in vivo... (Review)
Review
Mitochondrial dysfunction is implicated in the pathogenesis of diabetic kidney disease (DKD). Compared to the vast body of evidence from preclinical in vitro and in vivo studies, evidence from human studies is limited. In a comprehensive search of the published literature, findings from studies that reported evidence of mitochondrial dysfunction in individuals with DKD were examined. Three electronic databases (PubMed, Embase, and Scopus) were searched in March 2022. A total of 1339 articles were identified, and 22 articles met the inclusion criteria. Compared to non-diabetic controls (NDC) and/or individuals with diabetes but without kidney disease (DC), individuals with DKD (age ~55 years; diabetes duration ~15 years) had evidence of mitochondrial dysfunction. Individuals with DKD had evidence of disrupted mitochondrial dynamics (11 of 11 articles) uncoupling (2 of 2 articles), oxidative damage (8 of 8 articles), decreased mitochondrial respiratory capacity (1 of 1 article), decreased mtDNA content (5 of 6 articles), and decreased antioxidant capacity (3 of 4 articles) compared to ND and/or DC. Neither diabetes nor glycemic control explained these findings, but rather presence and severity of DKD may better reflect degree of mitochondrial dysfunction in this population. Future clinical studies should include individuals closer to diagnosis of diabetes to ascertain whether mitochondrial dysfunction is implicated in the development of, or is a consequence of, DKD.
Topics: Antioxidants; Diabetes Mellitus; Diabetic Nephropathies; Humans; Middle Aged; Mitochondria; Mitochondrial Dynamics; Oxidative Stress
PubMed: 36010558
DOI: 10.3390/cells11162481 -
Journal of Cellular Physiology Jul 2022Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of...
Hepatic fibrosis is a reversible response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by excessive deposition of extracellular matrix resulting in liver dysfunction and cirrhosis. Melatonin (N-acetyl-5-methoxytryptamine), the main product secreted by the pineal gland, is a multitasking indolamine with important physiological functions such as anti-inflammatory and antioxidant actions, modulation of circadian rhythms, and immune system enhancement. Among the numerous biological activities of melatonin, its antifibrotic effects have received increasingly more attention. In this study, we performed a systematic review of publications of the last 10 years evaluating the mechanisms of action of melatonin against liver fibrosis. The study protocol was registered at PROSPERO (CRD42022304744). Literature research was performed employing PubMed, Scopus, and Web of Science (WOS) databases, and after screening, 29 articles were included. Results from the selected studies provided denoted the useful actions of melatonin on the development, progression, and evolution of liver fibrosis. Melatonin antifibrotic effects in the liver involved the reduction of profibrogenic markers and modulation of several cellular processes and molecular pathways, mainly acting as an antioxidant and anti-inflammatory agent. In addition, the indolamine influenced different molecular processes, such as hepatocyte apoptosis, modulation of autophagy and mitophagy, restoration of circadian rhythms, and modulation of microRNAs, among others. Although some limitations have been found regarding variability in the study design, the findings here summarized display the potential role of melatonin in ameliorating the development of liver fibrosis and its possible progression to liver cirrhosis and hepatocarcinoma.
Topics: Anti-Inflammatory Agents; Antioxidants; Humans; Liver Cirrhosis; Melatonin
PubMed: 35404472
DOI: 10.1002/jcp.30735 -
Plants (Basel, Switzerland) Dec 2021The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities... (Review)
Review
The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called "erysenegalensein", only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.
PubMed: 35009024
DOI: 10.3390/plants11010019 -
Frontiers in Molecular Neuroscience 2021This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural... (Review)
Review
Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies.
This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for studies) and the TOXRTOOL checklist (for studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome , caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808). [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].
PubMed: 35002619
DOI: 10.3389/fnmol.2021.778569 -
Neurological Sciences : Official... Nov 2021Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that affects 1% of the population worldwide. Etiology of PD is likely to be... (Review)
Review
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that affects 1% of the population worldwide. Etiology of PD is likely to be multi-factorial such as protein misfolding, mitochondrial dysfunction, oxidative stress, and neuroinflammation that contributes to the pathology of Parkinson's disease (PD), numerous studies have shown that mitochondrial dysfunction may play a key role in the dopaminergic neuronal loss. In multiple ways, the two most important are the activation of neuroinflammation and mitochondrial dysfunction, while mitochondrial dysfunction could cause neuroinflammation and vice versa. Thus, the mitochondrial proteins are the highly promising target for the development of PD. However, the limited amount of dopaminergic neurons prevented the detailed investigation of Parkinson's disease with regard to mitochondrial dysfunction. Both genetic and environmental factors are also associated with mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provide direct evidence linking mitochondrial dysfunction to PD. A decrease of mitochondrial complex I activity is observed in PD brain and in neurotoxin- or genetic factor-induced in vitro and in vivo models. Moreover, PINK1, Parkin, DJ-1 and LRRK2 mitochondrial PD gene products have important roles in mitophagy, a cellular process that clear damaged mitochondria. This review paper would discuss the evidence for the mitochondrial dysfunction and neuroinflammation in PD.
Topics: Dopaminergic Neurons; Humans; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Parkinson Disease
PubMed: 34480241
DOI: 10.1007/s10072-021-05551-1 -
Biomedicines Aug 2021This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control... (Review)
Review
This systematic review sought to determine the effects of treadmill exercise on the neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease. PubMed, Web of Science, and EMBASE databases were searched through March 2020. The English-published animal studies that mentioned the effects of treadmill exercise on neural mitochondria in Parkinson's disease were included. The CAMARADES checklist was used to assess the methodological quality of the studies. Ten controlled trials were included (median CAMARADES score = 5.7/10) with various treadmill exercise durations (1-18 weeks). Seven studies analyzed the neural mitochondrial respiration, showing that treadmill training attenuated complex I deficits, cytochrome c release, ATP depletion, and complexes II-V abnormalities in Parkinson's disease. Nine studies analyzed the neural mitochondrial quality-control, reporting that treadmill exercise improved mitochondrial biogenesis, mitochondrial fusion, and mitophagy in Parkinson's disease. The review findings supported the hypothesis that treadmill training could attenuate both neural mitochondrial respiratory deficiency and neural mitochondrial quality-control dysregulation in Parkinson's disease, suggesting that treadmill training might slow down the progression of Parkinson's disease.
PubMed: 34440215
DOI: 10.3390/biomedicines9081011 -
Frontiers in Aging Neuroscience 2021Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's...
Parkin-mediated mitophagy is the dominant mitophagy pathway of neural cells. Its restoration will result in prevention of cognitive decline, including Alzheimer's disease (AD). The role of this mitophagy pathway in neurodegenerative diseases has drawn attention in recent years. The two main pathological proteins in AD, amyloid β (Aβ) and human Tau (hTau), interfere with mitochondrial dynamics through several pathways. However, taking into consideration the specific interactions between Aβ/hTau and Parkin, special focus is required on this mitophagy pathway and AD. In this review, these interactions are fully discussed, and an overview of the neuroprotective drugs that enhance Parkin-mediated mitophagy is presented. This systematic review was performed according to PRISMA guidelines, and a comprehensive literature search was done in the electronic databases up to September 2020, using search terms in the titles and abstracts to identify relevant studies. One hundred eighty-six articles were found, and 113 articles were screened by title and abstract. Finally, 25 articles were included in this systematic review according to our inclusion and exclusion criteria. Accumulation of Aβ and hTau affects mitophagy, including Parkin-mediated. Tau seems to prevent Parkin translocation directly. A Parkin level in the cell appears to be of importance in determining the damage caused by Aβ and hTau and in the future therapeutic approaches. Parkin controls the PINK1 level the presenillins, suggesting that mutations in presenillins affect Parkin mitophagy. Parkin mitophagy is a process affected by several AD pathological events multidimensionally.
PubMed: 34393755
DOI: 10.3389/fnagi.2021.674071 -
Theranostics 2021Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and...
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Topics: Autophagy; Humans; Macroautophagy; Mitophagy; Organelles
PubMed: 33391472
DOI: 10.7150/thno.49860