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https://www.readbyqxmd.com/read/28346404/chemical-screening-identifies-atm-as-a-target-for-alleviating-senescence
#1
Hyun Tae Kang, Joon Tae Park, Kobong Choi, Yongsub Kim, Hyo Jei Claudia Choi, Chul Won Jung, Young-Sam Lee, Sang Chul Park
Senescence, defined as irreversible cell-cycle arrest, is the main driving force of aging and age-related diseases. Here, we performed high-throughput screening to identify compounds that alleviate senescence and identified the ataxia telangiectasia mutated (ATM) inhibitor KU-60019 as an effective agent. To elucidate the mechanism underlying ATM's role in senescence, we performed a yeast two-hybrid screen and found that ATM interacted with the vacuolar ATPase V1 subunits ATP6V1E1 and ATP6V1G1. Specifically, ATM decreased E-G dimerization through direct phosphorylation of ATP6V1G1...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28345467/mitochondrial-dna-alteration-in-primary-and-metastatic-colorectal-cancer-different-frequency-and-association-with-selected-clinicopathological-and-molecular-markers
#2
Britta Kleist, Thuja Meurer, Micaela Poetsch
This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345280/otoprotective-effects-of-mouse-nerve-growth-factor-in-dba-2j-mice-with-early-onset-progressive-hearing-loss
#3
Qingzhu Wang, Hongchun Zhao, Tihua Zheng, Wenjun Wang, Xiaolin Zhang, Andi Wang, Bo Li, Yanfei Wang, Qingyin Zheng
As it displays progressive hair-cell loss and degeneration of spiral ganglion neurons (SGNs) characterized by early-onset progressive hearing loss (ePHL), DBA/2J is an inbred mouse strain widely used in hearing research. Mouse nerve growth factor (mNGF), as a common exogenous nerve growth factor (NGF), has been studied extensively for its ability to promote neuronal survival and growth. To determine whether mNGF can ameliorate progressive hearing loss (PHL) in DBA/2J mice, saline or mNGF was given to DBA/2J mice of either sex by daily intramuscular injection from the 1st to the 9th week after birth...
March 27, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28345160/increasing-skeletal-muscle-carnitine-availability-does-not-alter-the-adaptations-to-high-intensity-interval-training
#4
Christopher E Shannon, Reza Ghasemi, Paul L Greenhaff, Francis B Stephens
Increasing skeletal muscle carnitine availability alters muscle metabolism during steady-state exercise in healthy humans. We investigated whether elevating muscle carnitine, and thereby the acetyl-group buffering capacity, altered the metabolic and physiological adaptations to 24 weeks of high-intensity interval training (HIIT) at 100% maximal exercise capacity (Wattmax ). Twenty-one healthy male volunteers (age 23±2 years; BMI 24.2±1.1 kg/m(2) ) performed 2x3 minute bouts of cycling exercise at 100% Wattmax , separated by five minutes rest...
March 27, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28340313/linkage-between-mitochondrial-genome-alterations-telomere-length-and-aging-population
#5
Egija Zole, Krista Zadinane, Liana Pliss, Renate Ranka
We studied telomere length (TL) and mitochondrial DNA (mtDNA) copy number variations in individuals from Latvian Caucasian population in different age groups. We showed a positive correlation between TL and mtDNA copy number in individuals of up to 90 years of age; however, this correlation was not observed in the 90-100 years age group. While TL shortened with age and mtDNA content decreased with increasing age, in this study it was observed that mtDNA copy number in nonagenarians was slightly higher than in the 60-89 years age group...
March 24, 2017: Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis
https://www.readbyqxmd.com/read/28338606/dystrophic-cardiomyopathy-potential-role-of-calcium-in-pathogenesis-treatment-and-novel-therapies
#6
REVIEW
Victoria P A Johnstone, Helena M Viola, Livia C Hool
Duchenne muscular dystrophy (DMD) is caused by defects in the DMD gene and results in progressive wasting of skeletal and cardiac muscle due to an absence of functional dystrophin. Cardiomyopathy is prominent in DMD patients, and contributes significantly to mortality. This is particularly true following respiratory interventions that reduce death rate and increase ambulation and consequently cardiac load. Cardiomyopathy shows an increasing prevalence with age and disease progression, and over 95% of patients exhibit dilated cardiomyopathy by the time they reach adulthood...
March 24, 2017: Genes
https://www.readbyqxmd.com/read/28336790/prioritizing-functional-capacity-as-a-principal-end-point-for-therapies-oriented-to-older-adults-with-cardiovascular-disease-a-scientific-statement-for-healthcare-professionals-from-the-american-heart-association
#7
REVIEW
Daniel E Forman, Ross Arena, Rebecca Boxer, Mary A Dolansky, Janice J Eng, Jerome L Fleg, Mark Haykowsky, Arshad Jahangir, Leonard A Kaminsky, Dalane W Kitzman, Eldrin F Lewis, Jonathan Myers, Gordon R Reeves, Win-Kuang Shen
Adults are living longer, and cardiovascular disease is endemic in the growing population of older adults who are surviving into old age. Functional capacity is a key metric in this population, both for the perspective it provides on aggregate health and as a vital goal of care. Whereas cardiorespiratory function has long been applied by cardiologists as a measure of function that depended primarily on cardiac physiology, multiple other factors also contribute, usually with increasing bearing as age advances...
March 23, 2017: Circulation
https://www.readbyqxmd.com/read/28336486/mitochondrial-dysfunction-in-airway-disease
#8
Y S Prakash, Christina M Pabelick, Gary C Sieck
There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore non-canonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke and environmental insults important in these diseases, and in turn can respond to such stimuli via altered mitochondrial protein expression, structure, and resultant dysfunction...
March 21, 2017: Chest
https://www.readbyqxmd.com/read/28336424/the-impact-of-oxidative-stress-and-inflammation-on-rpe-degeneration-in-non-neovascular-amd
#9
REVIEW
Sayantan Datta, Marisol Cano, Katayoon Ebrahimi, Lei Wang, James T Handa
The retinal pigment epithelium (RPE) is a highly specialized, unique epithelial cell that interacts with photoreceptors on its apical side and with Bruch's membrane and the choriocapillaris on its basal side. Due to vital functions that keep photoreceptors healthy, the RPE is essential for maintaining vision. With aging and the accumulated effects of environmental stresses, the RPE can become dysfunctional and die. This degeneration plays a central role in age-related macular degeneration (AMD) pathobiology, the leading cause of blindness among the elderly in western societies...
March 20, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28334613/role-of-mitochondrial-metabolism-in-the-control-of-early-lineage-progression-and-aging-phenotypes-in-adult-hippocampal-neurogenesis
#10
Ruth Beckervordersandforth, Birgit Ebert, Iris Schäffner, Jonathan Moss, Christian Fiebig, Jaehoon Shin, Darcie L Moore, Laboni Ghosh, Mariela F Trinchero, Carola Stockburger, Kristina Friedland, Kathrin Steib, Julia von Wittgenstein, Silke Keiner, Christoph Redecker, Sabine M Hölter, Wei Xiang, Wolfgang Wurst, Ravi Jagasia, Alejandro F Schinder, Guo-Li Ming, Nicolas Toni, Sebastian Jessberger, Hongjun Song, D Chichung Lie
No abstract text is available yet for this article.
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334504/redd1-deficiency-impairs-autophagy-and-mitochondrial-biogenesis-in-articular-cartilage-and-increases-the-severity-of-experimental-osteoarthritis
#11
Oscar Alvarez-Garcia, Tokio Matsuzaki, Merissa Olmer, Lars Plate, Jeffery W Kelly, Martin K Lotz
Objective REDD1 is an endogenous inhibitor of mTOR that regulates cellular stress responses. REDD1 expression is decreased in aged and osteoarthritis (OA) cartilage and it regulates mTOR signaling and autophagy in articular chondrocytes in vitro. The present study investigated the effects of REDD1 deletion in vivo using a mouse model of experimental OA. Methods Severity of OA was histologically assessed in 4-month-old wild-type and in Redd1(-/-) mice subjected to surgical destabilization of the medial meniscus (DMM)...
March 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28333293/intra-individual-purifying-selection-on-mitochondrial-dna-variants-during-human-oogenesis
#12
Sara De Fanti, Saverio Vicario, Martin Lang, Domenico Simone, Cristina Magli, Donata Luiselli, Luca Gianaroli, Giovanni Romeo
Study Question: Does selection for mtDNA mutations occur in human oocytes? Summary Answer: We provide statistical evidence in favor of the existence of purifying selection for mtDNA mutations in human oocytes acting between the expulsion of the first and second polar bodies (PBs). What is Known Already: Several lines of evidence in Metazoa, including humans, indicate that variation within the germline of mitochondrial genomes is under purifying selection...
March 9, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28332767/bcap31-associated-encephalopathy-and-complex-movement-disorder-mimicking-mitochondrial-encephalopathy
#13
Saleh Albanyan, Amal Al Teneiji, Nasim Monfared, Saadet Mercimek-Mahmutoglu
BCAP31, encoded by BCAP31, is involved in the export of transmembrane proteins from the endoplasmic reticulum. Pathogenic variants in BCAP31 results in global developmental delay, dystonia, deafness and dysmorphic features in males, called deafness, dystonia, and cerebral hypomyelination (DDCH) syndrome. We report a new patient with BCAP3-associated encephalopathy, DDCH syndrome, sensorineural hearing loss, generalized dystonia, and choreoathetosis. This 3.5-year-old boy had microcephaly and failure to thrive within the first 3 months of life...
March 23, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28332488/parkinson-disease
#14
REVIEW
Werner Poewe, Klaus Seppi, Caroline M Tanner, Glenda M Halliday, Patrik Brundin, Jens Volkmann, Anette-Eleonore Schrag, Anthony E Lang
Parkinson disease is the second-most common neurodegenerative disorder that affects 2-3% of the population ≥65 years of age. Neuronal loss in the substantia nigra, which causes striatal dopamine deficiency, and intracellular inclusions containing aggregates of α-synuclein are the neuropathological hallmarks of Parkinson disease. Multiple other cell types throughout the central and peripheral autonomic nervous system are also involved, probably from early disease onwards. Although clinical diagnosis relies on the presence of bradykinesia and other cardinal motor features, Parkinson disease is associated with many non-motor symptoms that add to overall disability...
March 23, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28331386/phylogenetic-analysis-of-the-genus-laparocerus-with-comments-on-colonisation-and-diversification-in-macaronesia-coleoptera-curculionidae-entiminae
#15
Antonio Machado, Eduardo Rodríguez-Expósito, Mercedes López, Mariano Hernández
The flightless Entiminae weevil genus Laparocerus is the species-richest genus, with 237 species and subspecies, inhabiting Macaronesia (Madeira archipelago, Selvagens, Canary Islands) and the continental 'Macaronesian enclave' in Morocco (one single polytypic species). This is the second contribution to gain insight of the genus and assist in its systematic revision with a mitochondrial phylogenetic analysis. It centres on the Canarian clade, adding the 12S rRNA gene to the combined set of COII and 16S rRNA used in our first contribution on the Madeiran clade (here re-analysed)...
2017: ZooKeys
https://www.readbyqxmd.com/read/28331100/microrna-434-3p-regulates-age-related-apoptosis-through-eif5a1-in-the-skeletal-muscle
#16
Patricia S Pardo, Ameena Hajira, Aladin M Boriek, Junaith S Mohamed
Sarcopenia is caused by increased activation of catabolic pathways, including apoptosis. However, the mechanism underlying sarcopenia is not well understood. We report that aging alters miRNA expression profile as evidenced by miRNA microarray and real-time PCR. Our data show that miR-434-3p is highly downregulated miRNA in skeletal muscles of the aging mouse and provided the first evidence that miR-434 is a novel regulator of apoptosis. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and that inhibitory role of miR-434-3p was abolished by its antagomir, suggesting a role for miR-434-3p in apoptosis...
March 22, 2017: Aging
https://www.readbyqxmd.com/read/28330689/evaluation-of-methohexital-as-an-alternative-to-propofol-in-a-high-volume-outpatient-pediatric-sedation-service
#17
Nicholas E Jones, Michael S Kelleman, Harold K Simon, Jana A Stockwell, Courtney McCracken, Michael D Mallory, Pradip P Kamat
BACKGROUND: Propofol is a preferred agent for many pediatric sedation providers because of its rapid onset and short duration of action. It allows for quick turn around times and enhanced throughput. Occasionally, intravenous (IV) methohexital (MHX), an ultra-short acting barbiturate is utilized instead of propofol. OBJECTIVE: Describe the experience with MHX in a primarily propofol driven outpatient sedation program and to see if it serves as an acceptable alternative when propofol is not the preferred pharmacologic option...
March 8, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28330601/mitochondria-in-cell-senescence-is-mitophagy-the-weakest-link
#18
REVIEW
Viktor I Korolchuk, Satomi Miwa, Bernadette Carroll, Thomas von Zglinicki
Cell senescence is increasingly recognized as a major contributor to the loss of health and fitness associated with aging. Senescent cells accumulate dysfunctional mitochondria; oxidative phosphorylation efficiency is decreased and reactive oxygen species production is increased. In this review we will discuss how the turnover of mitochondria (a term referred to as mitophagy) is perturbed in senescence contributing to mitochondrial accumulation and Senescence-Associated Mitochondrial Dysfunction (SAMD). We will further explore the subsequent cellular consequences; in particular SAMD appears to be necessary for at least part of the specific Senescence-Associated Secretory Phenotype (SASP) and may be responsible for tissue-level metabolic dysfunction that is associated with aging and obesity...
March 14, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28329339/interrelations-between-mitochondrial-dna-copy-number-and-inflammation-in-older-adults
#19
I-Chien Wu, Cheng-Chieh Lin, Chin-San Liu, Chih-Cheng Hsu, Ching-Yu Chen, Chao A Hsiung
Background: Interplays between inflammation and mitochondrial biology are reported. Here, we examined the cross-sectional interrelationships of mitochondrial DNA copy number (mtDNACN) and inflammation and their interaction with physical functioning. Methods: A total of 1990 community-dwelling adults aged 65 years and older who were participating in the Healthy Aging Longitudinal Study in Taiwan underwent measurements of peripheral-blood leukocytes MtDNACN, multiple inflammatory markers, grip strength, and gait speed...
March 11, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28329151/caloric-restriction-and-rapamycin-differentially-alter-energy-metabolism-in-yeast
#20
Kyung-Mi Choi, Seok-Jin Hong, Jan M van Deursen, Sooah Kim, Kyoung Heon Kim, Cheol-Koo Lee
Rapamycin (RM), a drug that inhibits the mechanistic target of rapamycin (mTOR) pathway and responds to nutrient availability, seemingly mimics the effects of caloric restriction (CR) on healthy life span. However, the extent of the mechanistic overlap between RM and CR remains incompletely understood. Here, we compared the impact of CR and RM on cellular metabolic status. Both regimens maintained intracellular ATP through the chronological aging process and showed enhanced mitochondrial capacity. Comparative transcriptome analysis showed that CR had a stronger impact on global gene expression than RM...
March 8, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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