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mitochondrial and aging

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https://www.readbyqxmd.com/read/28827794/isocitrate-protects-dj-1-null-dopaminergic-cells-from-oxidative-stress-through-nadp-dependent-isocitrate-dehydrogenase-idh
#1
Jinsung Yang, Min Ju Kim, Woongchang Yoon, Eun Young Kim, Hyunjin Kim, Yoonjeong Lee, Boram Min, Kyung Shin Kang, Jin H Son, Hwan Tae Park, Jongkyeong Chung, Hyongjong Koh
DJ-1 is one of the causative genes for early onset familiar Parkinson's disease (PD) and is also considered to influence the pathogenesis of sporadic PD. DJ-1 has various physiological functions which converge on controlling intracellular reactive oxygen species (ROS) levels. In RNA-sequencing analyses searching for novel anti-oxidant genes downstream of DJ-1, a gene encoding NADP+-dependent isocitrate dehydrogenase (IDH), which converts isocitrate into α-ketoglutarate, was detected. Loss of IDH induced hyper-sensitivity to oxidative stress accompanying age-dependent mitochondrial defects and dopaminergic (DA) neuron degeneration in Drosophila, indicating its critical roles in maintaining mitochondrial integrity and DA neuron survival...
August 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28827409/genomic-and-functional-integrity-of-the-hematopoietic-system-requires-tolerance-of-oxidative-dna-lesions
#2
Ana Martín-Pardillos, Anastasia Tsaalbi-Shtylik, Si Chen, Seka Lazare, Ronald P van Os, Albertina Dethmers-Ausema, Nima Borhan Fakouri, Matthias Bosshard, Rossana Aprigliano, Barbara van Loon, Daniela C F Salvatori, Keiji Hashimoto, Celia Dingemanse-van der Spek, Masaaki Moriya, Lene Juel Rasmussen, Gerald de Haan, Marc H G P Raaijmakers, Niels de Wind
Endogenous DNA damage is causally associated with the functional decline and transformation of stem cells that characterize ageing. DNA lesions that have escaped DNA repair can induce replication stress and genomic breaks that induce senescence and apoptosis. It is not clear how stem and proliferating cells cope with accumulating endogenous DNA lesions, and how these ultimately affect the physiology of cells and tissues. Here we have addressed these questions by investigating the hematopoietic system of mice deficient for Rev1, a core factor in DNA translesion synthesis (TLS), the post-replicative bypass of damaged nucleotides...
August 21, 2017: Blood
https://www.readbyqxmd.com/read/28822845/triphenyl-phosphonium-coated-nano-quercetin-for-oral-delivery-neuroprotective-effects-in-attenuating-age-related-global-moderate-cerebral-ischemia-reperfusion-injury-in-rats
#3
Swarupa Ghosh, Sibani Sarkar, Somsubhra T Choudhury, Tirtha Ghosh, Nirmalendu Das
Cerebral ischemia-reperfusion is a classic example of reactive oxygen species (ROS) mediated acute damage to brain. Post-ischemic reperfusion induced oxygen free radicals production causes damage to brain cell mitochondria. Antioxidants like quercetin (Qc) have potentials to manage oxidative stress related pathophysiology. However low oral bioavailability and poor cell membrane permeability restrict its therapeutic efficacy. To overcome these hurdles mitochondria specific delivery of Qc nanocapsules was designed to efficiently counteract cerebral ischemia-reperfusion induced cell death and neurodegeneration in young and aged rats...
August 16, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28821956/effects-of-ageing-on-pro-arrhythmic-ventricular-phenotypes-in-incrementally-paced-murine-pgc-1%C3%AE-hearts
#4
Shiraz Ahmad, Haseeb Valli, Charlotte E Edling, Andrew A Grace, Kamalan Jeevaratnam, Christopher L-H Huang
A range of chronic clinical conditions accompany cardiomyocyte energetic dysfunction and constitute independent risk factors for cardiac arrhythmia. We investigated pro-arrhythmic and arrhythmic phenotypes in energetically deficient C57BL mice with genetic ablation of the mitochondrial promoter peroxisome proliferator-activated receptor-γ coactivator-1β (Pgc-1β), a known model of ventricular arrhythmia. Pro-arrhythmic and cellular action potential (AP) characteristics were compared in intact Langendorff-perfused hearts from young (12-16 week) and aged (> 52 week), wild-type (WT) and Pgc-1β (-/-) mice...
August 18, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28821228/sg-adviser-mtdna-a-web-server-for-mitochondrial-dna-annotation-with-data-from-200-samples-of-a-healthy-aging-cohort
#5
Manuel Rueda, Ali Torkamani
BACKGROUND: Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians...
August 18, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28819942/study-of-the-relationship-between-ages-and-oxidative-stress-damage-to-trophoblast-cell-mitochondria
#6
Lingling Jiang, Jianying Yan, Lixiang Wu
OBJECTIVES: To study the influence of AGEs on placental trophoblast mitochondria oxidative stress, and to explore the possible pathogenesis which may participate in pre-eclampsia. MATERIAL AND METHODS: Human trophoblast cells from early pregnancy were cultured by an enzyme-digestion method. When trophoblast cells reached approximately 70-80% after passages, they were incubated with pre-eclampsia serum for 24 hours. A fluorescent dye assay was applied to measure the mitochondrial membrane potential; ELISA was used to measure the activity of the mitochondrial permeability transition pore...
2017: Ginekologia Polska
https://www.readbyqxmd.com/read/28819266/amalaki-rasayana-a-traditional-indian-drug-enhances-cardiac-mitochondrial-and-contractile-functions-and-improves-cardiac-function-in-rats-with-hypertrophy
#7
Vikas Kumar, Kumar A Aneesh, K Kshemada, Kumar G S Ajith, Raj S S Binil, Neha Deora, G Sanjay, A Jaleel, T S Muraleedharan, E M Anandan, R S Mony, M S Valiathan, Kumar T R Santhosh, C C Kartha
We evaluated the cardioprotective effect of Amalaki Rasayana (AR), a rejuvenating Ayurvedic drug prepared from Phyllanthus emblica fruits in the reversal of remodeling changes in pressure overload left ventricular cardiac hypertrophy (LVH) and age-associated cardiac dysfunction in male Wistar rats. Six groups (aging groups) of 3 months old animals were given either AR or ghee and honey (GH) orally; seventh group was untreated. Ascending aorta was constricted using titanium clips in 3 months old rats (N = 24; AC groups) and after 6 months, AR or GH was given for further 12 months to two groups; one group was untreated...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818596/cardiometabolic-phenotypes-and-mitochondrial-dna-copy-number-in-two-cohorts-of-uk-women
#8
Anna L Guyatt, Kimberley Burrows, Philip A I Guthrie, Sue Ring, Wendy McArdle, Ian N M Day, Raimondo Ascione, Debbie A Lawlor, Tom R Gaunt, Santiago Rodriguez
The mitochondrial genome is present at variable copy number between individuals. Mitochondria are vulnerable to oxidative stress, and their dysfunction may be associated with cardiovascular disease. The association of mitochondrial DNA copy number with cardiometabolic risk factors (lipids, glycaemic traits, inflammatory markers, anthropometry and blood pressure) was assessed in two independent cohorts of European origin women, one in whom outcomes were measured at mean (SD) age 30 (4.3) years (N=2278) and the second at 69...
August 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28815872/a-multimethod-computational-simulation-approach-for-investigating-mitochondrial-dynamics-and-dysfunction-in-degenerative-aging
#9
Timothy E Hoffman, Katherine J Barnett, Lyle Wallis, William H Hanneman
Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans...
August 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/28815529/mitochondrial-associated-membranes-in-parkinson-s-disease
#10
Nobutaka Hattori, Taku Arano, Taku Hatano, Akio Mori, Yuzuru Imai
Parkinson's disease (PD) is a common neurodegenerative disorder, with ageing being a major risk factor. Accordingly, estimates predict an increasing number of PD patients due to our expanding life span. Consequently, developing a true disease-modifying therapy is necessary. In this regard, monogenic PD offers a suitable means for determining pathogenesis. Among monogenic forms of PD, mitochondrial dysfunction may be a major cause and is also likely to be involved in sporadic PD. Thus, mitochondrial impairment may be a common pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814984/protective-mechanisms-of-the-mitochondrial-derived-peptide-humanin-in-oxidative-and-endoplasmic-reticulum-stress-in-rpe-cells
#11
REVIEW
Leonid Minasyan, Parameswaran G Sreekumar, David R Hinton, Ram Kannan
Age-related macular degeneration (AMD) is the leading cause of severe and irreversible vision loss and is characterized by progressive degeneration of the retina resulting in loss of central vision. The retinal pigment epithelium (RPE) is a critical site of pathology of AMD. Mitochondria and the endoplasmic reticulum which lie in close anatomic proximity to each other are targets of oxidative stress and endoplasmic reticulum (ER) stress, respectively, and contribute to the progression of AMD. The two organelles exhibit close interactive function via various signaling mechanisms...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28813700/regenerative-medicine-approaches-for-age-related-muscle-loss-and-sarcopenia-a-mini-review
#12
Juan Diego Naranjo, Jenna L Dziki, Stephen F Badylak
Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia...
August 17, 2017: Gerontology
https://www.readbyqxmd.com/read/28813576/joint-analysis-of-nuclear-and-mitochondrial-variants-in-age-related-macular-degeneration-identifies-novel-loci-trpm1-and-abhd2-rlbp1
#13
Patrice J Persad, Iris M Heid, Daniel E Weeks, Paul N Baird, Eiko K de Jong, Jonathan L Haines, Margaret A Pericak-Vance, William K Scott
Purpose: Presently, 52 independent nuclear single nucleotide polymorphisms (nSNPs) have been associated with age-related macular degeneration (AMD) but their effects do not explain all its variance. Genetic interactions between the nuclear and mitochondrial (mt) genome may unearth additional genetic loci previously unassociated with AMD risk. Methods: Joint effects of nSNPs and selected mtSNPs were analyzed by two degree of freedom (2df) joint tests of association in the International AMD Genomics Consortium (IAMDGC) dataset (17,832 controls and 16,144 advanced AMD cases of European ancestry)...
August 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28813483/muroid-rodent-phylogenetics-900-species-tree-reveals-increasing-diversification-rates
#14
Scott J Steppan, John J Schenk
We combined new sequence data for more than 300 muroid rodent species with our previously published sequences for up to five nuclear and one mitochondrial genes to generate the most widely and densely sampled hypothesis of evolutionary relationships across Muroidea. An exhaustive screening procedure for publically available sequences was implemented to avoid the propagation of taxonomic errors that are common to supermatrix studies. The combined data set of carefully screened sequences derived from all available sequences on GenBank with our new data resulted in a robust maximum likelihood phylogeny for 900 of the approximately 1,620 muroids...
2017: PloS One
https://www.readbyqxmd.com/read/28812649/decreased-male-reproductive-success-in-association-with-mitochondrial-dysfunction
#15
Mika H Martikainen, John P Grady, Yi Shiau Ng, Charlotte L Alston, Grainne S Gorman, Robert W Taylor, Robert McFarland, Doug M Turnbull
The reproductive success of men with mitochondrial disease is to date unreported. We compared the age- and era-adjusted reproductive success of 94 British male patients with mitochondrial disease to that of the UK general male population. The reproductive success of men with mitochondrial disease was 65% of that in the general population (95% confidence interval: 53%; 79%), and the effect magnitude was related to the disease severity. This contrasts with the two previous studies finding that the reproductive success of women with mitochondrial DNA disease is not impaired...
August 16, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/28811869/pro-and-antioxidant-functions-of-the-peroxisome-mitochondria-connection-and-its-impact-on-aging-and-disease
#16
REVIEW
Amparo Pascual-Ahuir, Sara Manzanares-Estreder, Markus Proft
Peroxisomes and mitochondria are the main intracellular sources for reactive oxygen species. At the same time, both organelles are critical for the maintenance of a healthy redox balance in the cell. Consequently, failure in the function of both organelles is causally linked to oxidative stress and accelerated aging. However, it has become clear that peroxisomes and mitochondria are much more intimately connected both physiologically and structurally. Both organelles share common fission components to dynamically respond to environmental cues, and the autophagic turnover of both peroxisomes and mitochondria is decisive for cellular homeostasis...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28811861/importance-of-distinguishing-between-mitochondrial-encephalomyopathy-with-elderly-onset-of-stroke-like-episodes-and-cerebral-infarction
#17
Syuichi Tetsuka, Asako Tagawa, Tomoko Ogawa, Mieko Otsuka, Ritsuo Hashimoto, Hiroyuki Kato
The most common disease-causing mitochondrial DNA (mtDNA) mutation in mitochondrial encephalomyopathy (ME) with lactic acidosis and stroke-like episodes (MELAS) is m.3243A>G. In the future, the incidence of patients with cerebral infarction and diabetes mellitus is expected to increase tremendously. Additionally, the A3243G mutation typical of diabetes is estimated to be present in approximately 2% of all diabetes patients, which suggests that the potential disease population with a mitochondrial disorder is greater than previously thought, and there may have been many cases among the elderly that were misdiagnosed...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28811200/globular-adiponectin-reverses-osteo-sarcopenia-and-altered-body-composition-in-ovariectomized-rats
#18
Shyamsundar Pal China, Subhashis Pal, Sourav Chattopadhyay, Konica Porwal, Sapana Kushwaha, Sharmishtha Bhattacharyya, Monika Mittal, Anagha A Gurjar, Tarun Barbhuyan, Abhishek K Singh, Arun K Trivedi, Jiaur R Gayen, Sabyasachi Sanyal, Naibedya Chattopadhyay
Adiponectin regulates various metabolic processes including glucose flux, lipid breakdown and insulin response. We recently reported that adiponectin receptor1 (adipoR1) activation by a small molecule reverses osteopenia in leptin receptor deficient db/db (diabetic) mice. However, the role of adiponectin in bone metabolism under the setting of post-menopausal (estrogen-deficiency) osteopenia and associated metabolic derangements has not been studied. Here, we studied the therapeutic effect of the globular form of adiponectin (gAd), which is predominantly an adipoR1 agonist, in aged ovariectomized (OVX) rats and compared it with standard-of-care anti-osteoporosis drugs...
August 12, 2017: Bone
https://www.readbyqxmd.com/read/28809938/perinatal-testosterone-exposure-potentiates-vascular-dysfunction-by-er%C3%AE-suppression-in-endothelial-progenitor-cells
#19
Weiguo Xie, Mingming Ren, Ling Li, Yin Zhu, Zhigang Chu, Zhigang Zhu, Qiongfang Ruan, Wenting Lou, Haimou Zhang, Zhen Han, Xiaodong Huang, Wei Xiang, Tao Wang, Paul Yao
Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect...
2017: PloS One
https://www.readbyqxmd.com/read/28808499/epigenetics-and-oxidative-stress-in-aging
#20
REVIEW
Amy Guillaumet-Adkins, Yania Yañez, Manuel D Peris-Diaz, Ines Calabria, Cora Palanca-Ballester, Juan Sandoval
Aging is a multifactorial process characterized by the progressive loss of physiological functions, leading to an increased vulnerability to age-associated diseases and finally to death. Several theories have been proposed to explain the nature of aging. One of the most known identifies the free radicals produced by the mitochondrial metabolism as the cause of cellular and DNA damage. However, there are also several evidences supporting that epigenetic modifications, such as DNA methylation, noncoding RNAs, and histone modifications, play a critical role in the molecular mechanism of aging...
2017: Oxidative Medicine and Cellular Longevity
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