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https://www.readbyqxmd.com/read/29474864/a-crucial-role-of-rock-for-alleviation-of-senescence-associated-phenotype
#1
Joon Tae Park, Hyun Tae Kang, Chi Hyun Park, Young-Sam Lee, Kyung A Cho, Sang Chul Park
In our previous study, we uncovered a novel mechanism in which amelioration of Hutchinson-Gilford progeria syndrome (HGPS) phenotype is mediated by mitochondrial functional recovery upon rho-associated protein kinase (ROCK) inhibition. However, it remains elusive whether this mechanism is also applied to the amelioration of normal aging cells. In this study, we used Y-27632 and fasudil as effective ROCK inhibitors, and examined their role in senescence. We found that ROCK inhibition induced the functional recovery of the mitochondria as well as the metabolic reprogramming, which are two salient features that are altered in normal aging cells...
February 20, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29474453/detection-of-mitochondrial-dna-with-4977-bp-deletion-in-leukocytes-of-patients-with-ischemic-stroke
#2
Yu-Hua Huang, Chiung-Mei Chen, Yun-Shien Lee, Kuo-Hsuan Chang, Huei-Wen Chen, Yi-Chun Chen
BACKGROUND: Coronary artery disease is associated with a common mitochondrial DNA alteration, a 4977 bp deletion (mtDNA4977). The role of mtDNA4977 in ischemic stroke is unknown. METHODS: Real-time quantitative PCR was performed to quantify total mtDNA and mtDNA4977 in leukocytes in 283 ischemic stroke cases and 135 controls. Ratios of mtDNA4977 to total-mtDNA and total-mtDNA to nuclear-DNA were calculated. Nested PCR and Sanger sequencing were used to confirm undetectable levels of mtDNA4977...
2018: PloS One
https://www.readbyqxmd.com/read/29473507/oxidative-stress-and-decreased-mitochondrial-superoxide-dismutase-2-and-peroxiredoxin-1-and-4-based-mechanism-of-concurrent-activation-of-ampk-and-mtor-in-alzheimer-s-disease
#3
Shohreh Majd, John H T Power
BACKGROUND: Emerging evidence supports the hypothesis that metabolism dysfunction is involved in pathogenesis of Alzheimer's disease (AD). One aspect of metabolic dysfunction includes dysregulation of adenosine monophosphate kinase protein kinase (AMPK) and mammalian target of rapamycin (mTOR) metabolic axis, which is extensively present in some of the leading causes of AD such as cerebrovascular diseases, type 2 diabetes and brain ischaemic events. While the molecular basis underlying this metabolic dysregulation remains a significant challenge, mitochondrial dysfunction due to aging appears to be an essential factor to activate AMPK/mTOR signaling pathway, leading to abnormal neuronal energy metabolism and AD pathology...
February 22, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29472597/role-of-autophagy-in-modulating-post-maturation-aging-of-mouse-oocytes
#4
Fei-Hu Lin, Wei-Ling Zhang, Hong Li, Xiao-Dan Tian, Jie Zhang, Xiao Li, Chuan-Yong Li, Jing-He Tan
Mechanisms for post-maturation oocyte aging (PMOA) are not fully understood, and whether autophagy plays any role in PMOA is unknown. To explore the role of autophagy in PMOA, expression of autophagosomes and effects of the autophagy (macro-autophagy) activity on PMOA were observed in mouse oocytes. Oocyte activation rates and active caspase-3 levels increased continuously from 0 to 18 h of in vitro aging. While levels of microtubule-associated protein light chain 3 (LC3)-II increased up to 12 h and decreased thereafter, contents of p62 decreased from 0 to 12 h and then elevated to basal level by 18 h...
February 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29472048/oral-lichen-planus-differential-diagnoses-serum-autoantibodies-hematinic-deficiencies-and-management
#5
REVIEW
Chun-Pin Chiang, Julia Yu-Fong Chang, Yi-Ping Wang, Yu-Hsueh Wu, Shin-Yu Lu, Andy Sun
Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions...
February 19, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29468564/early-presymptomatic-changes-in-the-proteome-of-mitochondria-associated-membrane-in-the-app-ps1-mouse-model-of-alzheimer-s-disease
#6
Katalin Völgyi, Kata Badics, Fernando J Sialana, Péter Gulyássy, Edina Brigitta Udvari, Viktor Kis, László Drahos, Gert Lubec, Katalin Adrienna Kékesi, Gábor Juhász
Intracellular β-amyloid (Aβ) accumulation is an early event in Alzheimer's disease (AD) progression. Recently, it has been uncovered that presenilins (PSs), the key components of the amyloid precursor protein (APP) processing and the β-amyloid producing γ-secretase complex, are highly enriched in a special sub-compartment of the endoplasmic reticulum (ER) functionally connected to mitochondria, called mitochondria-associated ER membrane (MAM). A current hypothesis of pathogenesis of Alzheimer's diseases (AD) suggests that MAM is involved in the initial phase of AD...
February 22, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29467464/loss-of-the-drosophila-m-aaa-mitochondrial-protease-paraplegin-results-in-mitochondrial-dysfunction-shortened-lifespan-and-neuronal-and-muscular-degeneration
#7
Gautam Pareek, Ruth E Thomas, Leo J Pallanck
The progressive accumulation of dysfunctional mitochondria is implicated in aging and in common diseases of the elderly. To oppose this occurrence, organisms employ a variety of strategies, including the selective degradation of oxidatively damaged and misfolded mitochondrial proteins. Genetic studies in yeast indicate that the ATPase Associated with diverse cellular Activities (AAA+ ) family of mitochondrial proteases account for a substantial fraction of this protein degradation, but their metazoan counterparts have been little studied, despite the fact that mutations in the genes encoding these proteases cause a variety of human diseases...
February 21, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29466466/family-history-and-obesity-in-youth-their-effect-on-acylcarnitine-aminoacids-metabolomics-and-non-alcoholic-fatty-liver-disease-nafld-structural-equation-modeling-approach
#8
Maria Elena Romero-Ibarguengoitia, Felipe Vadillo-Ortega, Augusto Enrique Caballero, Isabel Ibarra-González, Arturo Herrera-Rosas, María Fabiola Serratos-Canales, Mireya León-Hernández, Antonio González-Chávez, Srinivas Mummidi, Ravindranath Duggirala, Juan Carlos López-Alvarenga
BACKGROUND: Structural equation modeling (SEM) can help understanding complex functional relationships among obesity, non-alcoholic fatty liver disease (NAFLD), family history of obesity, targeted metabolomics and pro-inflammatory markers. We tested two hypotheses: 1) If obesity precedes an excess of free fatty acids that increase oxidative stress and mitochondrial dysfunction, there would be an increase of serum acylcarnitines, amino acids and cytokines in obese subjects. Acylcarnitines would be related to non-alcoholic fatty disease that will induce insulin resistance...
2018: PloS One
https://www.readbyqxmd.com/read/29466320/dynamin-related-protein-1-at-the-crossroads-of-cancer
#9
REVIEW
Ana Rita Lima, Liliana Santos, Marcelo Correia, Paula Soares, Manuel Sobrinho-Simões, Miguel Melo, Valdemar Máximo
Mitochondrial dynamics are known to have an important role in so-called age-related diseases, including cancer. Mitochondria is an organelle involved in many key cellular functions and responds to physiologic or stress stimuli by adapting its structure and function. Perhaps the most important structural changes involve mitochondrial dynamics (fission and fusion), which occur in normal cells as well as in cells under dysregulation, such as cancer cells. Dynamin-related protein 1 (DRP1), a member of the dynamin family of guanosine triphosphatases (GTPases), is the key component of mitochondrial fission machinery...
February 21, 2018: Genes
https://www.readbyqxmd.com/read/29464849/in-vitro-protective-effects-of-an-aqueous-extract-of-clitoria-ternatea-l-flower-against-hydrogen-peroxide-induced-cytotoxicity-and-uv-induced-mtdna-damage-in-human-keratinocytes
#10
N N A Zakaria, E J Okello, M-J Howes, M A Birch-Machin, A Bowman
The traditional practice of eating the flowers of Clitoria ternatea L. or drinking their infusion as herbal tea in some of the Asian countries is believed to promote a younger skin complexion and defend against skin aging. This study was conducted to investigate the protective effect of C. ternatea flower water extract (CTW) against hydrogen peroxide-induced cytotoxicity and ultraviolet (UV)-induced mitochondrial DNA (mtDNA) damage in human keratinocytes. The protective effect against hydrogen peroxide-induced cytotoxicity was determined by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, and mtDNA damage induced by UV was determined by polymerase chain reaction...
February 21, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29464268/reversible-dilation-of-cerebral-macrovascular-changes-in-melas-episodes
#11
Yuxin Li, Weixingzi Xu, Chong Sun, Jie Lin, Jianxun Qu, Jiawen Cao, Haiqing Li, Liqin Yang
PURPOSE: To investigate the cerebral macrovascular changes as well as the relationship of large vessels and cerebral blood flow (CBF) in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) using magnetic resonance angiography (MRA) and arterial spin labeling (ASL) perfusion MR imaging (MRI). METHODS: A total of 20 patients diagnosed with MELAS (12 males, 8 females; mean age, 23.3 years) underwent conventional MRI, time-of-flight (TOF) MRA and three dimensional ASL...
February 20, 2018: Clinical Neuroradiology
https://www.readbyqxmd.com/read/29463847/small-vessel-vasculopathy-due-to-aberrant-autophagy-in-lamp-2-deficiency
#12
Huan T Nguyen, Satoru Noguchi, Kazuma Sugie, Yoshiyuki Matsuo, Chuyen T H Nguyen, Hitoshi Koito, Ichiro Shiojima, Ichizo Nishino, Hiroyasu Tsukaguchi
Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2-deficient mice and cultured cells...
February 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29461942/atp-synthase-a-target-for-dementia-and-aging
#13
James W Larrick, Jasmine W Larrick, Andrew R Mendelsohn
Advancing age is the biggest risk factor for development for the major life-threatening diseases in industrialized nations accounting for >90% of deaths. Alzheimer's dementia (AD) is among the most devastating. Currently approved therapies fail to slow progression of the disease, providing only modest improvements in memory. Recently reported work describes mechanistic studies of J147, a promising therapeutic molecule previously shown to rescue the severe cognitive deficits exhibited by aged, transgenic AD mice...
February 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29461488/blood-mononuclear-cell-mitochondrial-respiratory-chain-complex-iv-activity-is-decreased-in-multiple-sclerosis-patients-effects-of-%C3%AE-interferon-treatment
#14
Iain Hargreaves, Nimesh Mody, John Land, Simon Heales
OBJECTIVES: Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment...
February 20, 2018: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29459894/idiopathic-pulmonary-fibrosis-aging-mitochondrial-dysfunction-and-cellular-bioenergetics
#15
REVIEW
Daniel C Zank, Marta Bueno, Ana L Mora, Mauricio Rojas
At present, the etiology of idiopathic pulmonary fibrosis (IPF) remains elusive. Over the past two decades, however, researchers have identified and described the underlying processes that result in metabolic dysregulation, metabolic reprogramming, and mitochondrial dysfunction observed in the cells of IPF lungs. Metabolic changes and mitochondrial dysfunction in IPF include decreased efficiency of electron transport chain function with increasing production of reactive oxygen species, decreased mitochondrial biogenesis, and impaired mitochondrial macroautophagy, a key pathway for the removal of dysfunctional mitochondria...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29459830/coenzyme-q-10-supplementation-in-aging-and-disease
#16
REVIEW
Juan D Hernández-Camacho, Michel Bernier, Guillermo López-Lluch, Plácido Navas
Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29459695/light-action-spectrum-on-oxidative-stress-and-mitochondrial-damage-in-a2e-loaded-retinal-pigment-epithelium-cells
#17
Mélanie Marie, Karine Bigot, Claire Angebault, Coralie Barrau, Pauline Gondouin, Delphine Pagan, Stéphane Fouquet, Thierry Villette, José-Alain Sahel, Guy Lenaers, Serge Picaud
AIMS: Blue light is an identified risk factor for age-related macular degeneration (AMD). We investigated oxidative stress markers and mitochondrial changes in A2E-loaded retinal pigment epithelium cells under the blue-green part of the solar spectrum that reaches the retina to better understand the mechanisms underlying light-elicited toxicity. RESULTS: Primary retinal pigment epithelium cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a custom-made illumination device that delivers 10 nm-wide light bands, we demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen peroxide (H2 O2 ) and superoxide anion (O2 •- ) when exposed to blue-violet light...
February 19, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29454364/cyclosporine-a-does-not-prevent-second-eye-involvement-in-leber-s-hereditary-optic-neuropathy
#18
Stéphanie Leruez, Christophe Verny, Dominique Bonneau, Vincent Procaccio, Guy Lenaers, Patrizia Amati-Bonneau, Pascal Reynier, Clarisse Scherer, Adriana Prundean, Christophe Orssaud, Xavier Zanlonghi, Marie-Bénédicte Rougier, Caroline Tilikete, Dan Miléa
BACKRGROUND: Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber's hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2...
February 17, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29453899/the-role-of-dna-pk-in-aging-and-energy-metabolism
#19
REVIEW
Jay H Chung
DNA-dependent protein kinase (DNA-PK) is a very large holoenzyme comprised of the p470 kDa DNA-PK catalytic subunit (DNA-PKcs ) and the Ku heterodimer consisting of the p86 (Ku 80) and p70 (Ku 70) subunits. It is best known for its non-homologous end joining (NHEJ) activity, which repairs double-strand DNA (dsDNA) breaks (DSBs). As expected, the absence of DNA-PK activity results in sensitivity to ionizing radiation, which generates DSBs and defect in lymphocyte development, which requires NHEJ of the V(D)J region in the immunoglobulin and T cell receptor loci...
February 17, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29453441/circulating-cell-free-mitochondrial-dna-but-not-leukocyte-mitochondrial-dna-copy-number-is-elevated-in-major-depressive-disorder
#20
Daniel Lindqvist, Owen M Wolkowitz, Martin Picard, Lars Ohlsson, Francesco S Bersani, Johan Fernström, Åsa Westrin, Christina M Hough, Jue Lin, Victor I Reus, Elissa S Epel, Synthia H Mellon
Major depressive disorder (MDD) has been linked to mitochondrial defects, which could manifest in mitochondrial DNA (mtDNA) polymorphisms or mutations. Additionally, copy number of mtDNA (mtDNA-cn) can be quantified in peripheral blood mononuclear cells (PBMC)s, indirectly reflecting cellular energetics, or in the circulating cell-free mtDNA (ccf-mtDNA) levels, which may reflect a fraction of the mitochondrial genome released during cellular stress. Few studies have examined ccf-mtDNA in MDD, and no studies have tested its relationship with intracellular mtDNA-cn or with antidepressant treatment response...
January 30, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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