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Aging Cell

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https://www.readbyqxmd.com/read/27896923/homocysteine-modulates-5-lipoxygenase-expression-level-via-dna-methylation
#1
Jian-Guo Li, Carlos Barrero, Sapna Gupta, Warren D Kruger, Salim Merali, Domenico Praticò
Elevated levels of homocysteinemia (Hcy), a risk factor for late-onset Alzheimer's disease (AD), have been associated with changes in cell methylation. Alzheimer's disease is characterized by an upregulation of the 5-lipoxygenase (5LO), whose promoter is regulated by methylation. However, whether Hcy activates 5LO enzymatic pathway by influencing the methylation status of its promoter remains unknown. Brains from mice with high Hcy were assessed for the 5LO pathway and neuronal cells exposed to Hcy implemented to study the mechanism(s) regulating 5LO expression levels and the effect on amyloid β formation...
November 29, 2016: Aging Cell
https://www.readbyqxmd.com/read/27790859/dimethyl-sulfide-protects-against-oxidative-stress-and-extends-lifespan-via-a-methionine-sulfoxide-reductase-a-dependent-catalytic-mechanism
#2
Xin-Lei Guan, Peng-Fei Wu, Sheng Wang, Juan-Juan Zhang, Zu-Cheng Shen, Han Luo, Hao Chen, Li-Hong Long, Jian-Guo Chen, Fang Wang
Methionine (Met) sulfoxide reductase A (MsrA) is a key endogenous antioxidative enzyme with longevity benefits in animals. Only very few approaches have been reported to enhance MsrA function. Recent reports have indicated that the antioxidant capability of MsrA may involve a Met oxidase activity that facilities the reaction of Met with reactive oxygen species (ROS). Herein, we used a homology modeling approach to search the substrates for the oxidase activity of MsrA. We found that dimethyl sulfide (DMS), a main metabolite that produced by marine algae, emerged as a good substrate for MsrA-catalytic antioxidation...
October 28, 2016: Aging Cell
https://www.readbyqxmd.com/read/27785870/senescence-associated-dna-methylation-is-stochastically-acquired-in-subpopulations-of-mesenchymal-stem-cells
#3
Julia Franzen, Anne Zirkel, Jonathon Blake, Björn Rath, Vladimir Benes, Argyris Papantonis, Wolfgang Wagner
Replicative senescence has a major impact on function and integrity of cell preparations. This process is reflected by continuous DNA methylation (DNAm) changes at specific CpG dinucleotides in the course of in vitro culture, and such modifications can be used to estimate the state of cellular senescence for quality control of cell preparations. Still, it is unclear how senescence-associated DNAm changes are regulated and whether they occur simultaneously across a cell population. In this study, we analyzed global DNAm profiles of human mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs) to demonstrate that senescence-associated DNAm changes are overall similar in these different cell types...
October 26, 2016: Aging Cell
https://www.readbyqxmd.com/read/27730721/lin-28-balances-longevity-and-germline-stem-cell-number-in-caenorhabditis-elegans-through-let-7-akt-daf-16-axis
#4
Dan Wang, Lei Hou, Shuhei Nakamura, Ming Su, Fang Li, Weiyang Chen, Yizhen Yan, Christopher D Green, Di Chen, Hong Zhang, Adam Antebi, Jing-Dong J Han
The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28...
October 11, 2016: Aging Cell
https://www.readbyqxmd.com/read/27723233/distinct-inflammatory-phenotypes-of-microglia-and-monocyte-derived-macrophages-in-alzheimer-s-disease-models-effects-of-aging-and-amyloid-pathology
#5
Elodie Martin, Céline Boucher, Bertrand Fontaine, Cécile Delarasse
Alzheimer's disease (AD) is a neurodegenerative disease characterized by formation of amyloid-β (Aβ) plaques, activated microglia, and neuronal cell death leading to progressive dementia. Recent data indicate that microglia and monocyte-derived macrophages (MDM) are key players in the initiation and progression of AD, yet their respective roles remain to be clarified. As AD occurs mostly in the elderly and aging impairs myeloid functions, we addressed the inflammatory profile of microglia and MDM during aging in TgAPP/PS1 and TgAPP/PS1dE9, two transgenic AD mouse models, compared to WT littermates...
October 8, 2016: Aging Cell
https://www.readbyqxmd.com/read/27709751/amyloid-%C3%AE-induced-astrogliosis-is-mediated-by-%C3%AE-1-integrin-via-nadph-oxidase-2-in-alzheimer-s-disease
#6
Ane Wyssenbach, Tania Quintela, Francisco Llavero, Jose L Zugaza, Carlos Matute, Elena Alberdi
Astrogliosis is a hallmark of Alzheimer's disease (AD) and may constitute a primary pathogenic component of that disorder. Elucidation of signaling cascades inducing astrogliosis should help characterizing the function of astrocytes and identifying novel molecular targets to modulate AD progression. Here, we describe a novel mechanism by which soluble amyloid-β modulates β1-integrin activity and triggers NADPH oxidase (NOX)-dependent astrogliosis in vitro and in vivo. Amyloid-β oligomers activate a PI3K/classical PKC/Rac1/NOX pathway which is initiated by β1-integrin in cultured astrocytes...
October 5, 2016: Aging Cell
https://www.readbyqxmd.com/read/27686631/dna-polymerase-%C3%AE-decrement-triggers-death-of-olfactory-bulb-cells-and-impairs-olfaction-in-a-mouse-model-of-alzheimer-s-disease
#7
Magdalena Misiak, Rebeca Vergara Greeno, Beverly A Baptiste, Peter Sykora, Dong Liu, Stephanie Cordonnier, Evandro F Fang, Deborah L Croteau, Mark P Mattson, Vilhelm A Bohr
Alzheimer's disease (AD) involves the progressive degeneration of neurons critical for learning and memory. In addition, patients with AD typically exhibit impaired olfaction associated with neuronal degeneration in the olfactory bulb (OB). Because DNA base excision repair (BER) is reduced in brain cells during normal aging and AD, we determined whether inefficient BER due to reduced DNA polymerase-β (Polβ) levels renders OB neurons vulnerable to degeneration in the 3xTgAD mouse model of AD. We interrogated OB histopathology and olfactory function in wild-type and 3xTgAD mice with normal or reduced Polβ levels...
September 30, 2016: Aging Cell
https://www.readbyqxmd.com/read/27686535/function-of-the-sirt3-mitochondrial-deacetylase-in-cellular-physiology-cancer-and-neurodegenerative-disease
#8
REVIEW
Aneesa Ansari, Md Shahedur Rahman, Subbroto K Saha, Forhad K Saikot, Akash Deep, Ki-Hyun Kim
In mammals, seven members of the sirtuin protein family known as class III histone deacetylase have been identified for their characteristic features. These distinguished characteristics include the tissues where they are distributed or located, enzymatic activities, molecular functions, and involvement in diseases. Among the sirtuin members, SIRT3 has received much attention for its role in cancer genetics, aging, neurodegenerative disease, and stress resistance. SIRT3 controls energy demand during stress conditions such as fasting and exercise as well as metabolism through the deacetylation and acetylation of mitochondrial enzymes...
September 29, 2016: Aging Cell
https://www.readbyqxmd.com/read/27683245/antioxidants-reveal-an-inverted-u-shaped-dose-response-relationship-between-reactive-oxygen-species-levels-and-the-rate-of-aging-in-caenorhabditis-elegans
#9
David Desjardins, Briseida Cacho-Valadez, Ju-Ling Liu, Ying Wang, Callista Yee, Kristine Bernard, Arman Khaki, Lionel Breton, Siegfried Hekimi
Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions...
September 28, 2016: Aging Cell
https://www.readbyqxmd.com/read/27683205/uncoupling-associations-of-risk-alleles-with-endophenotypes-and-phenotypes-insights-from-the-apob-locus-and-heart-related-traits
#10
Alexander M Kulminski, Yelena Kernogitski, Irina Culminskaya, Yury Loika, Konstantin G Arbeev, Olivia Bagley, Matt Duan, Liubov Arbeeva, Svetlana V Ukraintseva, Deqing Wu, Eric Stallard, Anatoliy I Yashin
Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogeneous, age-related traits driven by the elusive role of evolution in their properties. We analyzed in detail the associations of rs693 and rs562338 polymorphisms representing the Apolipoprotein B locus with endophenotypes (total cholesterol [TC] and high-density lipoprotein cholesterol) and phenotypes (myocardial infarction [MI] and survival) in four large-scale studies, which include 20 748 individuals with 2357 MI events...
September 28, 2016: Aging Cell
https://www.readbyqxmd.com/read/27660103/activated-monocytes-resist-elimination-by-retinal-pigment-epithelium-and-downregulate-their-otx2-expression-via-tnf-%C3%AE
#11
Thibaud Mathis, Michael Housset, Chiara Eandi, Fanny Beguier, Sara Touhami, Sacha Reichman, Sebastien Augustin, Pauline Gondouin, José-Alain Sahel, Laurent Kodjikian, Olivier Goureau, Xavier Guillonneau, Florian Sennlaub
Orthodenticle homeobox 2 (OTX2) controls essential, homeostatic retinal pigment epithelial (RPE) genes in the adult. Using cocultures of human CD14(+) blood monocytes (Mos) and primary porcine RPE cells and a fully humanized system using human-induced pluripotent stem cell-derived RPE cells, we show that activated Mos markedly inhibit RPEOTX2 expression and resist elimination in contact with the immunosuppressive RPE. Mechanistically, we demonstrate that TNF-α, secreted from activated Mos, mediates the downregulation of OTX2 and essential RPE genes of the visual cycle among others...
September 22, 2016: Aging Cell
https://www.readbyqxmd.com/read/27660040/dietary-rapamycin-supplementation-reverses-age-related-vascular-dysfunction-and-oxidative-stress-while-modulating-nutrient-sensing-cell-cycle-and-senescence-pathways
#12
Lisa A Lesniewski, Douglas R Seals, Ashley E Walker, Grant D Henson, Mark W Blimline, Daniel W Trott, Gary C Bosshardt, Thomas J LaRocca, Brooke R Lawson, Melanie C Zigler, Anthony J Donato
Inhibition of mammalian target of rapamycin, mTOR, extends lifespan and reduces age-related disease. It is not known what role mTOR plays in the arterial aging phenotype or if mTOR inhibition by dietary rapamycin ameliorates age-related arterial dysfunction. To explore this, young (3.8 ± 0.6 months) and old (30.3 ± 0.2 months) male B6D2F1 mice were fed a rapamycin supplemented or control diet for 6-8 weeks. Although there were few other notable changes in animal characteristics after rapamycin treatment, we found that glucose tolerance improved in old mice, but was impaired in young mice, after rapamycin supplementation (both P < 0...
September 22, 2016: Aging Cell
https://www.readbyqxmd.com/read/27653523/opposing-impacts-on-healthspan-and-longevity-by-limiting-dietary-selenium-in-telomere-dysfunctional-mice
#13
Ryan T Wu, Lei Cao, Elliot Mattson, Kenneth W Witwer, Jay Cao, Huawei Zeng, Xin He, Gerald F Combs, Wen-Hsing Cheng
Selenium (Se) is a trace metalloid essential for life, but its nutritional and physiological roles during the aging process remain elusive. While telomere attrition contributes to replicative senescence mainly through persistent DNA damage response, such an aging process is mitigated in mice with inherently long telomeres. Here, weanling third generation telomerase RNA component knockout mice carrying short telomeres were fed a Se-deficient basal diet or the diet supplemented with 0.15 ppm Se as sodium selenate to be nutritionally sufficient throughout their life...
September 21, 2016: Aging Cell
https://www.readbyqxmd.com/read/27633878/chelation-of-hippocampal-zinc-enhances-long-term-potentiation-and-synaptic-tagging-capture-in-ca1-pyramidal-neurons-of-aged-rats-implications-to-aging-and-memory
#14
Mahesh Shivarama Shetty, Mahima Sharma, Sreedharan Sajikumar
Aging is associated with decline in cognitive functions, prominently in the memory consolidation and association capabilities. Hippocampus plays a crucial role in the formation and maintenance of long-term associative memories, and a significant body of evidence shows that impairments in hippocampal function correlate with aging-related memory loss. A number of studies have implicated alterations in hippocampal synaptic plasticity, such as long-term potentiation (LTP), in age-related cognitive decline although exact mechanisms underlying are not completely clear...
September 16, 2016: Aging Cell
https://www.readbyqxmd.com/read/27633771/annexin-a1-restores-a%C3%AE-1-42-induced-blood-brain-barrier-disruption-through-the-inhibition-of-rhoa-rock-signaling-pathway
#15
Jong-Chan Park, Sung Hoon Baik, Sun-Ho Han, Hyun Jin Cho, Hyunjung Choi, Haeng Jun Kim, Heesun Choi, Wonik Lee, Dong Kyu Kim, Inhee Mook-Jung
The blood-brain barrier (BBB) is composed of brain capillary endothelial cells and has an important role in maintaining homeostasis of the brain separating the blood from the parenchyma of the central nervous system (CNS). It is widely known that disruption of the BBB occurs in various neurodegenerative diseases, including Alzheimer's disease (AD). Annexin A1 (ANXA1), an anti-inflammatory messenger, is expressed in brain endothelial cells and regulates the BBB integrity. However, its role and mechanism for protecting BBB in AD have not been identified...
September 16, 2016: Aging Cell
https://www.readbyqxmd.com/read/27628712/small-molecule-compounds-that-induce-cellular-senescence
#16
Nadezhda V Petrova, Artem K Velichko, Sergey V Razin, Omar L Kantidze
To date, dozens of stress-induced cellular senescence phenotypes have been reported. These cellular senescence states may differ substantially from each other, as well as from replicative senescence through the presence of specific senescence features. Here, we attempted to catalog virtually all of the cellular senescence-like states that can be induced by low molecular weight compounds. We summarized biological markers, molecular pathways involved in senescence establishment, and specific traits of cellular senescence states induced by more than fifty small molecule compounds...
September 14, 2016: Aging Cell
https://www.readbyqxmd.com/read/27623715/endogenous-reactive-oxygen-species-cause-astrocyte-defects-and-neuronal-dysfunctions-in-the-hippocampus-a-new-model-for-aging-brain
#17
Takamasa Ishii, Yumi Takanashi, Koichi Sugita, Masaki Miyazawa, Rintaro Yanagihara, Kayo Yasuda, Hiromi Onouchi, Noboru Kawabe, Munehiro Nakata, Yorihiro Yamamoto, Phil S Hartman, Naoaki Ishii
The etiology of astrocyte dysfunction is not well understood even though neuronal defects have been extensively studied in a variety of neuronal degenerative diseases. Astrocyte defects could be triggered by the oxidative stress that occurs during physiological aging. Here, we provide evidence that intracellular or mitochondrial reactive oxygen species (ROS) at physiological levels can cause hippocampal (neuronal) dysfunctions. Specifically, we demonstrate that astrocyte defects occur in the hippocampal area of middle-aged Tet-mev-1 mice with the SDHC(V69E) mutation...
September 13, 2016: Aging Cell
https://www.readbyqxmd.com/read/27619151/caloric-restriction-increases-brain-mitochondrial-calcium-retention-capacity-and-protects-against-excitotoxicity
#18
Ignacio Amigo, Sergio Luiz Menezes-Filho, Luis Alberto Luévano-Martínez, Bruno Chausse, Alicia J Kowaltowski
Caloric restriction (CR) protects against many cerebral pathological conditions that are associated with excitotoxic damage and calcium overload, although the mechanisms are still poorly understood. Here we show that CR strongly protects against excitotoxic insults in vitro and in vivo in a manner associated with significant changes in mitochondrial function. CR increases electron transport chain activity, enhances antioxidant defenses, and favors mitochondrial calcium retention capacity in the brain. These changes are accompanied by a decrease in cyclophilin D activity and acetylation and an increase in Sirt3 expression...
September 13, 2016: Aging Cell
https://www.readbyqxmd.com/read/27618784/mtor-regulates-the-expression-of-dna-damage-response-enzymes-in-long-lived-snell-dwarf-ghrko-and-pappa-ko-mice
#19
Graham Dominick, Jacqueline Bowman, Xinna Li, Richard A Miller, Gonzalo G Garcia
Studies of the mTOR pathway have prompted speculation that diminished mTOR complex-1 (mTORC1) function may be involved in controlling the aging process. Our previous studies have shown diminished mTORC1 activity in tissues of three long-lived mutant mice: Snell dwarf mice, growth hormone receptor gene disrupted mice (GHRKO), and in this article, mice deficient in the pregnancy-associated protein-A (PAPPA-KO). The ways in which lower mTOR signals slow aging and age-related diseases are, however, not well characterized...
September 13, 2016: Aging Cell
https://www.readbyqxmd.com/read/27613664/exercise-reverses-age-related-vulnerability-of-the-retina-to-injury-by-preventing-complement-mediated-synapse-elimination-via-a-bdnf-dependent-pathway
#20
Vicki Chrysostomou, Sandra Galic, Peter van Wijngaarden, Ian A Trounce, Gregory R Steinberg, Jonathan G Crowston
Retinal ganglion cells (RGCs) become increasingly vulnerable to injury with advancing age. We recently showed that this vulnerability can be strongly modified in mice by exercise. However, the characteristics and underlying mechanisms of retinal protection with exercise remain unknown. Hence, the aim of this study was to investigate cellular changes associated with exercise-induced protection of aging retinal cells and the role of local and peripheral trophic signalling in mediating these effects. We focussed on two molecules that are thought to play key roles in mediating beneficial effects of exercise: brain-derived neurotrophic factor (BDNF) and AMP-activated protein kinase (AMPK)...
September 9, 2016: Aging Cell
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