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Mitochondria AND aging

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https://www.readbyqxmd.com/read/28099989/effects-of-a-dietary-ketone-ester-on-hippocampal-glycolytic-and-tca-cycle-intermediates-and-amino-acids-in-a-3xtgad-mouse-model-of-alzheimer-s-disease
#1
Robert J Pawlosky, Martin F Kemper, Yoshihero Kashiwaya, M Todd King, Mark P Mattson, Richard L Veech
In patients with Alzheimer's disease (AD) and in a triple transgenic (3xTgAD) mouse model of AD low glucose metabolism in the brain precedes loss of memory and cognitive decline. The metabolism of ketones in the brain by-passes glycolysis and therefore may correct several deficiencies that are associated with glucose hypometabolism. A dietary supplement composed of an ester of D-β-hydroxybutyrate and R-1,3 butane diol referred to as ketone ester (KE) was incorporated into a rodent diet and fed to 3xTgAD mice for 8 months...
January 18, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28098219/combined-lrrk2-mutation-aging-and-chronic-low-dose-oral-rotenone-as-a-model-of-parkinson-s-disease
#2
Hui-Fang Liu, Philip Wing-Lok Ho, Gideon Chi-Ting Leung, Colin Siu-Chi Lam, Shirley Yin-Yu Pang, Lingfei Li, Michelle Hiu-Wai Kung, David Boyer Ramsden, Shu-Leong Ho
Aging, genetics and environmental toxicity are important etiological factors in Parkinson's disease (PD). However, its pathogenesis remains unclear. A major obstacle is the lack of an appropriate experimental model which incorporates genetic susceptibility, aging and prolonged environmental toxicity. Here, we explored the interplay amongst these factors using mutant LRRK2(R1441G) (leucine-rich-repeat-kinase-2) knockin mice. We found that mutant primary cortical and mesencephalic dopaminergic neurons were more susceptible to rotenone-induced ATP deficiency and cell death...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28094012/mammalian-mitochondria-and-aging-an-update
#3
REVIEW
Timo E S Kauppila, Johanna H K Kauppila, Nils-Göran Larsson
Mitochondria were first postulated to contribute to aging more than 40 years ago. During the following decades, multiple lines of evidence in model organisms and humans showed that impaired mitochondrial function can contribute to age-associated disease phenotypes and aging. However, in contrast to the original theory favoring oxidative damage as a cause for mtDNA mutations, there are now strong data arguing that most mammalian mtDNA mutations originate as replication errors made by the mtDNA polymerase. Currently, a substantial amount of mitochondrial research is focused on finding ways to either remove or counteract the effects of mtDNA mutations with the hope of extending the human health- and lifespan...
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28088333/mitochondrial-uncoupling-in-cancer-cells-liabilities-and-opportunities
#4
REVIEW
Gyorgy Baffy
Acquisition of the endosymbiotic ancestor of mitochondria was a critical event in eukaryote evolution. Mitochondria offered an unparalleled source of metabolic energy through oxidative phosphorylation and allowed the development of multicellular life. However, as molecular oxygen had become the terminal electron acceptor in most eukaryotic cells, the electron transport chain proved to be the largest intracellular source of superoxide, contributing to macromolecular injury, aging, and cancer. Hence, the 'contract of endosymbiosis' represents a compromise between the possibilities and perils of multicellular life...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087734/increased-mitophagy-in-the-skeletal-muscle-of-spinal-and-bulbar-muscular-atrophy-patients
#5
Doriana Borgia, Adriana Malena, Marco Spinazzi, Maria Andrea Desbats, Leonardo Salviati, Aaron P Russell, Giovanni Miotto, Laura Tosatto, Elena Pegoraro, Gianni Sorarù, Maria Pennuto, Lodovica Vergani
Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by polyglutamine expansion in the androgen receptor (AR) and characterized by the loss of lower motor neurons. Here we investigated pathological processes occurring in muscle biopsy specimens derived from SBMA patients and, as controls, age-matched healthy subjects and patients suffering from amyotrophic lateral sclerosis (ALS) and neurogenic atrophy. We detected atrophic fibers in the muscle of SBMA, ALS and neurogenic atrophy patients...
January 13, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28087333/nicotinamide-nucleotide-transhydrogenase-activity-impacts-mitochondrial-redox-balance-and-the-development-of-hypertension-in-mice
#6
Igor Leskov, Amber Neville, Xinggui Shen, Sibile Pardue, Christopher G Kevil, D Neil Granger, David M Krzywanski
Oxidant stress contributes to the initiation and progression of hypertension (HTN) by enhancing endothelial dysfunction and/or causing perturbations in nitric oxide homeostasis. Differences in mitochondrial function may augment this process and provide insight into why age of onset and clinical outcomes differ among individuals from distinct ethnic groups. We have previously demonstrated that variation in normal mitochondrial function and oxidant production exists in endothelial cells from individuals of Caucasian and African-American ethnicity and that this variation contributes to endothelial dysfunction...
December 16, 2016: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/28074272/-role-of-the-aging-visual-system-in-glaucoma
#7
J D Unterlauft, M R R Böhm
BACKGROUND: Glaucoma is the second leading cause of blindness worldwide and is usually diagnosed in higher age groups. The goal was to survey how patient age influences the development of glaucoma. MATERIALS AND METHODS: A web-based search on aging of the visual system and its influence on glaucoma was performed and the most important results are summarized. RESULTS: The prevalence of glaucoma rises with age. Aging processes of the trabecular meshwork and the uveoscleral outflow pathway lead to a rise in the intraocular pressure...
January 10, 2017: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/28067471/traditional-and-novel-tools-to-probe-the-mitochondrial-metabolism-in-health-and-disease
#8
REVIEW
Yanfei Zhang, José L Avalos
Mitochondrial metabolism links energy production to other essential cellular processes such as signaling, cellular differentiation, and apoptosis. In addition to producing adenosine triphosphate (ATP) as an energy source, mitochondria are responsible for the synthesis of a myriad of important metabolites and cofactors such as tetrahydrofolate, α-ketoacids, steroids, aminolevulinic acid, biotin, lipoic acid, acetyl-CoA, iron-sulfur clusters, heme, and ubiquinone. Furthermore, mitochondria and their metabolism have been implicated in aging and several human diseases, including inherited mitochondrial disorders, cardiac dysfunction, heart failure, neurodegenerative diseases, diabetes, and cancer...
January 9, 2017: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
https://www.readbyqxmd.com/read/28064117/differential-proteomic-and-oxidative-profiles-unveil-dysfunctional-protein-import-to-adipocyte-mitochondria-in-obesity-associated-aging-and-diabetes
#9
María Gómez-Serrano, Emilio Camafeita, Juan A López, Miguel A Rubio, Irene Bretón, Inés García-Consuegra, Eva García-Santos, Jesús Lago, Andrés Sánchez-Pernaute, Antonio Torres, Jesús Vázquez, Belén Peral
Human age-related diseases, including obesity and type 2 diabetes (T2DM), have long been associated to mitochondrial dysfunction; however, the role for adipose tissue mitochondria in these conditions remains unknown. We have tackled the impact of aging and T2DM on adipocyte mitochondria from obese patients by quantitating not only the corresponding abundance changes of proteins, but also the redox alterations undergone by Cys residues thereof. For that, we have resorted to a high-throughput proteomic approach based on isobaric labeling, liquid chromatography and mass spectrometry...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#10
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
January 4, 2017: Kidney International
https://www.readbyqxmd.com/read/28063379/oxidative-stress-mitochondrial-abnormalities-and-antioxidant-defense-in-ataxia-telangiectasia-bloom-syndrome-and-nijmegen-breakage-syndrome
#11
REVIEW
Mateusz Maciejczyk, Bozena Mikoluc, Barbara Pietrucha, Edyta Heropolitanska-Pliszka, Malgorzata Pac, Radosław Motkowski, Halina Car
Rare pleiotropic genetic disorders, Ataxia-telangiectasia (A-T), Bloom syndrome (BS) and Nijmegen breakage syndrome (NBS) are characterised by immunodeficiency, extreme radiosensitivity, higher cancer susceptibility, premature aging, neurodegeneration and insulin resistance. Some of these functional abnormalities can be explained by aberrant DNA damage response and chromosomal instability. It has been suggested that one possible common denominator of these conditions could be chronic oxidative stress caused by endogenous ROS overproduction and impairment of mitochondrial homeostasis...
December 28, 2016: Redox Biology
https://www.readbyqxmd.com/read/28061861/oxidative-status-predicts-quality-in-human-mesenchymal-stem-cells
#12
Alessandro Bertolo, Simona Capossela, Gion Fränkl, Martin Baur, Tobias Pötzel, Jivko Stoyanov
BACKGROUND: Human bone marrow-derived mesenchymal stem cells (MSC) are adult progenitor cells with great potential for application in cell-based therapies. From a cell-based therapy perspective, there are two limitations to MSC use: (1) these therapies require large numbers of cells, and long-term expansion of MSC in vitro promotes replicative senescence; and (2) patient variability is a challenge for defining MSC quality standards for transplantation. This study aimed to determine whether low or high oxidative status of MSC correlate with changes in cell expansion and differentiation potentials...
January 6, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28055007/dysfunctional-autophagy-in-rpe-a-contributing-factor-in-age-related-macular-degeneration
#13
Nady Golestaneh, Yi Chu, Yang-Yu Xiao, Gianna L Stoleru, Alexander C Theos
Age-related macular degeneration (AMD) is a devastating neurodegenerative disease and a major cause of blindness in the developed world. Owing to its complexity and the lack of an adequate human model that recapitulates key aspects of the disease, the molecular mechanisms of AMD pathogenesis remain poorly understood. Here we show that cultured human retinal pigment epithelium (RPE) from AMD donors (AMD RPE) are functionally impaired and exhibit distinct phenotypes compared with RPE cultured from normal donors (normal RPE)...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28045997/loss-of-boss-causes-shortened-lifespan-with-mitochondrial-dysfunction-in-drosophila
#14
Ayako Kohyama-Koganeya, Mizuki Kurosawa, Yoshio Hirabayashi
Aging is a universal process that causes deterioration in biological functions of an organism over its lifetime. There are many risk factors that are thought to contribute to aging rate, with disruption of metabolic homeostasis being one of the main factors that accelerates aging. Previously, we identified a new function for the putative G-protein-coupled receptor, Bride of sevenless (BOSS), in energy metabolism. Since maintaining metabolic homeostasis is a critical factor in aging, we investigated whether BOSS plays a role in the aging process...
2017: PloS One
https://www.readbyqxmd.com/read/28045767/autophagy-in-hepatocytes-in-infants-with-alpha-1-atd-and-different-liver-disease-outcomes-a-retrospective-analysis
#15
Elżbieta Czarnowska, Agnieszka Bakuła, Joanna B Bierła, Justyna Niderla-Bielińska, Agnieszka Sowińska, Joanna Cielecka-Kuszyk, Piotr Socha
OBJECTIVES: It is unclear whether a distinct activity of pathways removing the AT protein in Alpha-1-Antitrypsin Deficiency (α1ATD) are associated with an unfavorable predisposition toliver disease in the future. The aim of this study was to determine whether liverspecific activity of AT protein disposal occurs at infancy in α1ATD with PiZZ phenotype (ATZ). METHODS: Liver samples of 17 infants with unfavorable ATZ outcome (Group I, n = 8, median age  = 0...
December 30, 2016: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/28039571/identification-of-a-previously-undetected-metabolic-defect-in-the-complex-ii-caenorhabditis-elegans-mev-1-mutant-strain-using-respiratory-control-analysis
#16
Sheng Fong, Li Fang Ng, Li Theng Ng, Philip K Moore, Barry Halliwell, Jan Gruber
Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context. This parameter is traditionally measured using single-chamber Clark electrodes without the addition of metabolic modulators...
December 30, 2016: Biogerontology
https://www.readbyqxmd.com/read/28039397/physical-exercise-in-aging-human-skeletal-muscle-increases-mitochondrial-calcium-uniporter-expression-levels-and-affects-mitochondria-dynamics
#17
Sandra Zampieri, Cristina Mammucari, Vanina Romanello, Laura Barberi, Laura Pietrangelo, Aurora Fusella, Simone Mosole, Gaia Gherardi, Christian Höfer, Stefan Löfler, Nejc Sarabon, Jan Cvecka, Matthias Krenn, Ugo Carraro, Helmut Kern, Feliciano Protasi, Antonio Musarò, Marco Sandri, Rosario Rizzuto
Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca(2+) homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28027494/ultrastructural-evidence-for-impaired-mitochondrial-fission-in-the-aged-rhesus-monkey-dorsolateral-prefrontal-cortex
#18
Yury M Morozov, Dibyadeep Datta, Constantinos D Paspalas, Amy F T Arnsten
Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease...
December 10, 2016: Neurobiology of Aging
https://www.readbyqxmd.com/read/28018233/carbonic-anhydrase-iii-is-expressed-in-mouse-skeletal-muscles-independent-of-fiber-type-specific-myofilament-protein-isoforms-and-plays-a-role-in-fatigue-resistance
#19
Han-Zhong Feng, J-P Jin
Carbonic anhydrase III (CAIII) is a metabolic enzyme and a regulator for intracellular pH. CAIII has been reported with high level expression in slow twitch skeletal muscles. Here we demonstrate that CAIII is expressed in multiple slow and fast twitch muscles of adult mouse independent of the expression of myosin isoforms. Expressing similar fast type of myofilament proteins, CAIII-positive tibial anterior (TA) muscle exhibits higher tolerance to fatigue than that of CAIII-negative fast twitch extensor digitorum longus (EDL) muscle in in situ contractility studies...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/28018212/mitochondrial-functional-changes-characterization-in-young-and-senescent-human-adipose-derived-mscs
#20
Bernd R Stab, Laura Martinez, Adriana Grismaldo, Alejandra Lerma, María L Gutiérrez, Luis A Barrera, Jhon J Sutachan, Sonia L Albarracín
Mitochondria are highly dynamic organelles that in response to the cell's bio-energetic state continuously undergo structural remodeling fission and fusion processes. This mitochondrial dynamic activity has been implicated in cell cycle, autophagy, and age-related diseases. Adult tissue-derived mesenchymal stromal/stem cells present a therapeutic potential. However, to obtain an adequate mesenchymal stromal/stem cell number for clinical use, extensive in vitro expansion is required. Unfortunately, these cells undergo replicative senescence rapidly by mechanisms that are not well understood...
2016: Frontiers in Aging Neuroscience
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