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Mitochondria AND aging

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https://www.readbyqxmd.com/read/28543935/neurodegeneration-in-ataxia-telangiectasia-multiple-roles-of-atm-kinase-in-cellular-homeostasis
#1
REVIEW
Kay Rui Choy, Dianne J Watters
Ataxia-Telangiectasia (A-T) is characterized by neuronal degeneration, cancer, diabetes, immune deficiency and increased sensitivity to ionizing radiation. A-T is attributed to the deficiency of the protein kinase coded by the ATM (Ataxia-Telangiectasia Mutated) gene. ATM is a sensor of DNA Double Strand Breaks and signals to cell cycle checkpoints and the DNA repair machinery. ATM phosphorylates numerous substrates and activates many cell-signalling pathways. There has been considerable debate about whether a defective DNA damage response is causative of the neurological aspects of the disease...
May 22, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28543099/evidence-of-altered-mitochondrial-protein-expression-after-chronic-ethanol-consumption-in-the-aged-estrogen-deficient-female-rat-heart
#2
Alexandra M Garvin, J L Miller-Lee, D R Sharda, G M Kanski, J C Hunter, Donna H Korzick
BACKGROUND: Estrogen loss has been implicated to increase the risk of alcoholic cardiomyopathy in post-menopausal women. The purpose of this study was to identify novel mitochondrial protein targets for the treatment of alcoholic cardiomyopathy in aged women using a state-of-the-art proteomics approach. We hypothesized that chronic ethanol (EtOH) ingestion exacerbates maladaptive mitochondrial protein expression in the aged female heart METHODS: Adult (3 mo) and aged (18 mo) F344 ovary-intact or ovariectomized (OVX) rats were randomly assigned an EtOH or control Lieber-DeCarli 'all liquid' diet for 20 wks...
May 19, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28542339/bioenergetic-profile-of-human-coronary-artery-smooth-muscle-cells-and-effect-of-metabolic-intervention
#3
Mingming Yang, Amy E Chadwick, Caroline Dart, Tomoko Kamishima, John M Quayle
Bioenergetics of artery smooth muscle cells is critical in cardiovascular health and disease. An acute rise in metabolic demand causes vasodilation in systemic circulation while a chronic shift in bioenergetic profile may lead to vascular diseases. A decrease in intracellular ATP level may trigger physiological responses while dedifferentiation of contractile smooth muscle cells to a proliferative and migratory phenotype is often observed during pathological processes. Although it is now possible to dissect multiple building blocks of bioenergetic components quantitatively, detailed cellular bioenergetics of artery smooth muscle cells is still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28540446/lipid-per-oxidation-in-mitochondria-an-emerging-target-in-the-ageing-process
#4
REVIEW
O S Ademowo, H K I Dias, D G A Burton, H R Griffiths
Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation...
May 24, 2017: Biogerontology
https://www.readbyqxmd.com/read/28539682/the-human-body-as-an-energetic-hybrid-new-perspectives-for-chronic-disease-treatment
#5
REVIEW
Michał Gajewski, Przemysław Rzodkiewicz, Sławomir Maśliński
Inflammatory response is accompanied by changes in cellular energy metabolism. Proinflammatory mediators like plasma C-reactive protein, IL-6, plasminogen activator inhibitor-1, TNF-α or monocyte chemoattractant protein-1 released in the site of inflammation activates immune cells and increase energy consumption. Increased demand for energy creates local hypoxia and lead in consequence to mitochondrial dysfunction. Metabolism of cells is switched to anaerobic glycolysis. Mitochondria continuously generate free radicals that what result in imbalance that causes oxidative stress, which results in oxidative damage...
2017: Reumatologia
https://www.readbyqxmd.com/read/28538514/long-term-outcome-of-4-patients-with-transcobalamin-deficiency-caused-by-2-novel-tcn2-mutations
#6
Marwan Nashabat, Gustavo Maegawa, Peter H Nissen, Ebba Nexo, Hussain Al-Shamrani, Mohammed Al-Owain, Majid Alfadhel
Cobalamin (vitamin B12 [Cbl]) is an essential cofactor for many biochemical pathways. Transcobalamin (TC) is required to internalize Cbl into the cells through membrane receptor-mediated endocytosis. Cbl is then processed in the cytoplasm and mitochondria by complementation factors leading to its active metabolites; methylcobalamin and 5-deoxyadenosyl-cobalamin. Deficiency of TC results in an elevation in methylmalonic acid and homocysteine. Patients usually present with macrocytic anemia, pancytopenia, failure to thrive, gastrointestinal symptoms, and neurological dysfunction...
May 22, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28534301/effects-of-acetyl-l-carnitine-in-diabetic-neuropathy-and-other-geriatric-disorders
#7
REVIEW
G Sergi, S Pizzato, F Piovesan, C Trevisan, N Veronese, E Manzato
A long history of diabetes mellitus and increasing age are associated with the onset of diabetic neuropathy, a painful and highly disabling complication with a prevalence peaking at 50% among elderly diabetic patients. Acetyl-L-carnitine (ALC) is a molecule derived from the acetylation of carnitine in the mitochondria that has an essential role in energy production. It has recently been proposed as a therapy to improve the symptoms of diabetic neuropathy. ALC is widely distributed in mammalian tissues, including the brain, blood-brain barrier, brain neurons, and astrocytes...
May 22, 2017: Aging Clinical and Experimental Research
https://www.readbyqxmd.com/read/28533980/mitochondrial-complex-i-deficiency-leads-to-the-retardation-of-early-embryonic-development-in-ndufs4-knockout-mice
#8
Mei Wang, Ya-Ping Huang, Han Wu, Ke Song, Cong Wan, A-Ni Chi, Ya-Mei Xiao, Xiao-Yang Zhao
BACKGROUND: The NDUFS4 gene encodes an 18-kD subunit of mitochondria complex I, and mutations in this gene lead to the development of a severe neurodegenerative disease called Leigh syndrome (LS) in humans. To investigate the disease phenotypes and molecular mechanisms of Leigh syndrome, the Ndufs4 knockout (KO) mouse has been widely used as a novel animal model. Because the homozygotes cannot survive beyond child-bearing age, whether Ndufs4 and mitochondrial complex I influence early embryonic development remains unknown...
2017: PeerJ
https://www.readbyqxmd.com/read/28526334/regulatory-cis-and-trans-elements-of-mitochondrial-d-loop-driven-reporter-genes-in-budding-tunicates
#9
Kaz Kawamura, Yuhya Saitoh, Loriano Ballarin, Takeshi Sunanaga
To unveil the underlying mechanism of mitochondrial gene regulation associated with ageing and budding in the tunicate Polyandrocarpa misakiensis, mitochondrial non-coding-region (NCR)-containing reporter genes were constructed. PmNCR2.3K/GFP was expressed spatiotemporally in a pattern quite similar to mitochondrial 16SrRNA. The reporter gene expression was sensitive to high dose of rifampicin similar to mitochondrial genes, suggesting that the transcription indeed occurs in mitochondria. However, the gene expression also occurred in vivo in the cell nucleus and in vitro in the nuclear extracts...
May 16, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28523458/the-respiratory-chain-inhibitor-rotenone-affects-peroxisomal-dynamics-via-its-microtubule-destabilising-activity
#10
Josiah B Passmore, Sonia Pinho, Maria Gomez-Lazaro, Michael Schrader
Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling are supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics...
May 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28522903/oxidative-stress-antioxidants-and-intestinal-calcium-absorption
#11
REVIEW
Gabriela Diaz de Barboza, Solange Guizzardi, Luciana Moine, Nori Tolosa de Talamoni
The disequilibrium between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione (GSH) and GSH-dependent enzymes as major components...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522765/exercise-training-in-tg%C3%AE-q-44-mice-during-the-progression-of-chronic-heart-failure-cardiac-vs-peripheral-soleus-muscle-impairments-to-oxidative-metabolism
#12
Bruno Grassi, Joanna Majerczak, Eleonora Bardi, Alessia Buso, Marina Comelli, Stefan Chlopicki, Magdalena Guzik, Irene Mavelli, Zenon Nieckarz, Desy Salvadego, Urszula Tyrankiewicz, Tomasz Skorka, Roberto Bottinelli, Jerzy A Zoladz, Maria Antonietta Pellegrino
Cardiac function, skeletal (soleus) muscle oxidative metabolism and the effects of exercise training were evaluated in a transgenic murine model (Tgαq*44) of chronic heart failure (CHF) during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e. from 10 to 12 months of age). Forty-eight Tgαq*44 mice and 43 wild-type (WT) FVB controls were randomly assigned to control groups and to groups undergoing 2 months of intense exercise training (spontaneous running on a instrumented wheel)...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28511886/numtogenesis-as-a-mechanism-for-development-of-cancer
#13
REVIEW
Keshav K Singh, Aaheli Roy Choudhury, Hemant K Tiwari
Transfer of genetic material from cytoplasmic organelles to the nucleus, an ongoing process, has implications in evolution, aging, and human pathologies such as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis, defining the term as the transfer of mtDNA into the nuclear genome, or, less specifically, the transfer of mitochondria or mitochondrial components into the nucleus. There is increasing evidence of the involvement of NUMTs in human biology and pathology...
May 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28510636/impact-of-aging-on-calcium-signaling-and-membrane-potential-in-endothelium-of-resistance-arteries-a-role-for-mitochondria
#14
Erik J Behringer, Steven S Segal
Impaired blood flow to peripheral tissues during advanced age is associated with endothelial dysfunction and diminished bioavailability of nitric oxide (NO). However, it is unknown whether aging impacts coupling between intracellular calcium ([Ca2+]i) signaling and small- and intermediate K+ channel (SKCa/IKCa) activity during endothelium-derived hyperpolarization (EDH), a signaling pathway integral to dilation of the resistance vasculature. To address the potential impact of aging on EDH, Fura-2 photometry and intracellular recording were applied to evaluate [Ca2+]i and membrane potential of intact endothelial tubes (width, 60 µm; length, 1-3 mm) freshly isolated from superior epigastric arteries of young (4-6 mo) and old (24-26 mo) male C57BL/6 mice...
May 16, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28504707/regulation-of-mitochondrial-biogenesis-in-erythropoiesis-by-mtorc1-mediated-protein%C3%A2-translation
#15
Xin Liu, Yuannyu Zhang, Min Ni, Hui Cao, Robert A J Signer, Dan Li, Mushan Li, Zhimin Gu, Zeping Hu, Kathryn E Dickerson, Samuel E Weinberg, Navdeep S Chandel, Ralph J DeBerardinis, Feng Zhou, Zhen Shao, Jian Xu
Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification...
May 15, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28499984/systemic-pten-akt1-mtor-pathway-activity-in-patients-with-normal-tension-glaucoma-and-ocular-hypertension-a-case-series
#16
Gerassimos Lascaratos, Kai-Yin Chau, Haogang Zhu, Despoina Gkotsi, Deborah Kamal, Ivan Gout, Philip J Luthert, Anthony H V Schapira, David F Garway-Heath
Glaucoma is the most common optic neuropathy in humans and the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP), while increasing evidence suggests that systemic mitochondrial abnormalities may also be implicated in its pathogenesis. We have recently shown that patients who have not developed glaucoma despite being exposed for many years to high IOP (ocular hypertension - OHT) have more efficient mitochondria, measured in peripheral blood lymphocytes, when compared to age-similar controls and fast progressing normal tension glaucoma (NTG) patients...
May 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28499253/the-role-of-sodium-hydrosulfide-in-attenuating-the-aging-process-via-pi3k-akt-and-camkk%C3%AE-ampk-pathways
#17
Xubo Chen, Xueyan Zhao, Hua Cai, Haiying Sun, Yujuan Hu, Xiang Huang, Wen Kong, Weijia Kong
Age-related dysfunction of the central auditory system, known as central presbycusis, is characterized by defects in speech perception and sound localization. It is important to determine the pathogenesis of central presbycusis in order to explore a feasible and effective intervention method. Recent work has provided fascinating insight into the beneficial function of H2S on oxidative stress and stress-related disease. In this study, we investigated the pathogenesis of central presbycusis and tried to explore the mechanism of H2S action on different aspects of aging by utilizing a mimetic aging rat and senescent cellular model...
April 25, 2017: Redox Biology
https://www.readbyqxmd.com/read/28493603/age-related-endothelial-dysfunction-in-human-skeletal-muscle-feed-arteries-the-role-of-free-radicals-derived-from-mitochondria-in-the-vasculature
#18
Song-Young Park, Oh Sung Kwon, Robert H I Andtbacka, John R Hyngstrom, Van Reese, Michael P Murphy, Russell S Richardson
AIM: This study sought to determine the role of free radicals derived from mitochondria in the vasculature in the recognized age-related endothelial dysfunction of human skeletal muscle feed arteries (SMFAs). METHODS: A total of 44 SMFAs were studied with and without acute exposure to the mitochondria-targeted antioxidant MitoQ and nitric oxide synthase (NOS) blockade. The relative abundance of proteins from the electron transport chain, phosphorylated (p-) to endothelial (e) NOS ratio, manganese superoxide dismutase (MnSOD), and the mitochondria-derived superoxide (O2(-) ) levels were assessed in SMFA...
May 11, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28488455/intracellular-methylglyoxal-induces-oxidative-damage-to-pancreatic-beta-cell-line-ins-1-cell-through-ire1%C3%AE-jnk-and-mitochondrial-apoptotic-pathway
#19
Chongxiao Liu, Yanhong Huang, Yifan Zhang, Xueru Chen, Xiang Kong, Yan Dong
An increased intracellular methylglyoxal (MGO) under hyperglycemia led to pancreatic beta cell death. However, its mechanism in which way with MGO induced beta cell death remains unknown. We investigated both high glucose and MGO treatment significantly inclined intracellular MGO concentration and inhibited cell viability in vitro. MGO treatment also triggered intracellular advanced glycation end products (AGEs) formation, declined mitochondrial membrane potential (MMP), increased oxidative stress and the expression of ER stress mediators Grp78/Bip and p-PERK; activated mitochondrial apoptotic pathway, which could mimic by Glo1 knockdown...
May 10, 2017: Free Radical Research
https://www.readbyqxmd.com/read/28487632/nicotinamide-and-wld-s-act-together-to-prevent-neurodegeneration-in-glaucoma
#20
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Brynn H Cardozo, Kelly E Cochran, Simon W M John
Glaucoma is a complex neurodegenerative disease characterized by progressive visual dysfunction leading to vision loss. Retinal ganglion cells are the primary affected neuronal population, with a critical insult damaging their axons in the optic nerve head. This insult is typically secondary to harmfully high levels of intraocular pressure (IOP). We have previously determined that early mitochondrial abnormalities within retinal ganglion cells lead to neuronal dysfunction, with age-related declines in NAD (NAD(+) and NADH) rendering retinal ganglion cell mitochondria vulnerable to IOP-dependent stresses...
2017: Frontiers in Neuroscience
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