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rapamycin aging

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https://www.readbyqxmd.com/read/28229367/inhibition-of-mtor-pathway-by-rapamycin-decreases-p-glycoprotein-expression-and-spontaneous-seizures-in-pharmacoresistant-epilepsy
#1
Xiaosa Chi, Cheng Huang, Rui Li, Wei Wang, Mengqian Wu, Jinmei Li, Dong Zhou
The mammalian target of rapamycin (mTOR) has been demonstrated to mediate multidrug resistance in various tumors by inducing P-glycoprotein (P-gp) overexpression. Here, we investigated the correlation between the mTOR pathway and P-gp expression in pharmacoresistant epilepsy. Temporal cortex specimens were obtained from patients with refractory mesial temporal lobe epilepsy (mTLE) and age-matched controls who underwent surgeries at West China Hospital of Sichuan University between June 2014 and May 2015. We established a rat model of epilepsy kindled by coriaria lactone (CL) and screened pharmacoresistant rats (non-responders) using phenytoin...
February 22, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#2
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#3
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28183786/extracellular-rnas-are-associated-with-insulin-resistance-and-metabolic-phenotypes
#4
Ravi Shah, Venkatesh Murthy, Michael Pacold, Kirsty Danielson, Kahraman Tanriverdi, Martin G Larson, Kristina Hanspers, Alexander Pico, Eric Mick, Jared Reis, Sarah de Ferranti, Elizaveta Freinkman, Daniel Levy, Udo Hoffmann, Stavroula Osganian, Saumya Das, Jane E Freedman
OBJECTIVE: Insulin resistance (IR) is a hallmark of obesity and metabolic disease. Circulating extracellular RNAs (ex-RNAs), stable RNA molecules in plasma, may play a role in IR, though most studies on ex-RNAs in IR are small. We sought to characterize the relationship between ex-RNAs and metabolic phenotypes in a large community-based human cohort. RESEARCH DESIGN AND METHODS: We measured circulating plasma ex-RNAs in 2,317 participants without diabetes in the Framingham Heart Study (FHS) Offspring Cohort at cycle 8 and defined associations between ex-RNAs and IR (measured by circulating insulin level)...
February 9, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28178239/eprs-is-a-critical-mtorc1-s6k1-effector-that-influences-adiposity-in-mice
#5
Abul Arif, Fulvia Terenzi, Alka A Potdar, Jie Jia, Jessica Sacks, Arnab China, Dalia Halawani, Kommireddy Vasu, Xiaoxia Li, J Mark Brown, Jie Chen, Sara C Kozma, George Thomas, Paul L Fox
Metabolic pathways that contribute to adiposity and ageing are activated by the mammalian target of rapamycin complex 1 (mTORC1) and p70 ribosomal protein S6 kinase 1 (S6K1) axis. However, known mTORC1-S6K1 targets do not account for observed loss-of-function phenotypes, suggesting that there are additional downstream effectors of this pathway. Here we identify glutamyl-prolyl-tRNA synthetase (EPRS) as an mTORC1-S6K1 target that contributes to adiposity and ageing. Phosphorylation of EPRS at Ser999 by mTORC1-S6K1 induces its release from the aminoacyl tRNA multisynthetase complex, which is required for execution of noncanonical functions of EPRS beyond protein synthesis...
February 16, 2017: Nature
https://www.readbyqxmd.com/read/28177677/mtorc1-inhibitors-rapamycin-and-metformin-affect-cardiovascular-markers-differentially-in-zdf-rats
#6
Ravi Nistala, Ahmad Raja, Lakshmi Pulakat
Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. Here we investigated the differential effects of rapamycin (1.2mg/kg/day delivered subcutaneously for six weeks) and metformin (300mg/kg/day delivered orally for 11 weeks) treatments on male Zucker diabetic fatty (ZDF) rats that mimic the cardio-renal pathology of T2DM patients and progress to insulin insufficiency...
January 4, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28169477/localised-intravascular-coagulation-complicating-venous-malformations-in-children-associations-and-therapeutic-options
#7
REVIEW
Kevin Y Zhuo, Susan Russell, Orli Wargon, Susan Adams
Venous malformations are slow-flow congenital vascular malformations that enlarge as the child ages and may be associated with localised intravascular coagulation, a consumptive coagulopathy characterised by elevated D-dimer and decreased fibrinogen levels. The authors review the known correlations between localised intravascular coagulation and venous malformation number, size and planes involved, and call attention to the concept of the progression of localised intravascular coagulopathy as the child ages and their venous malformations enlarge...
February 7, 2017: Journal of Paediatrics and Child Health
https://www.readbyqxmd.com/read/28168445/regulation-of-the-h-atp-synthase-by-if1-a-role-in-mitohormesis
#8
REVIEW
Pau B Esparza-Moltó, Cristina Nuevo-Tapioles, José M Cuezva
The mitochondrial H(+)-ATP synthase is a primary hub of cellular homeostasis by providing the energy required to sustain cellular activity and regulating the production of signaling molecules that reprogram nuclear activity needed for adaption to changing cues. Herein, we summarize findings regarding the regulation of the activity of the H(+)-ATP synthase by its physiological inhibitor, the ATPase inhibitory factor 1 (IF1) and their functional role in cellular homeostasis. First, we outline the structure and the main molecular mechanisms that regulate the activity of the enzyme...
February 6, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28167236/rapamycin-and-the-inhibition-of-the-secretory-phenotype
#9
Rong Wang, Bharath Sunchu, Viviana I Perez
Senescent cells contribute to age-related pathology and loss of function, and their selective removal improves physiological function and extends longevity. Cell senescence is a complex process that can be triggered by multiple challenges. Recently it has been observed that the composition of the secretory phenotype or SASP depends on the insult that triggers cell senescence. Rapamycin, an inhibitor of mTOR that increases longevity in several species, inhibits cell senescence in vitro, while silencing the Nrf2 gene induces premature senescence...
February 4, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28154735/preventing-aging-with-stem-cell-rejuvenation-feasible-or-infeasible
#10
EDITORIAL
Kanya Honoki
Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches...
January 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28148781/the-amino-acid-metabolite-homocysteine-activates-mtorc1-to-inhibit-autophagy-and-form-abnormal-proteins-in-human-neurons-and-mice
#11
Khoosheh Khayati, Henri Antikainen, Edward M Bonder, Gregory F Weber, Warren D Kruger, Hieronim Jakubowski, Radek Dobrowolski
The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28134984/conversion-from-sirolimus-to-everolimus-in-long-term-liver-graft-recipients
#12
Nina Weiler, Nigar Bilge, Sven Troetschler, Johannes Vermehren, Andreas Anton Schnitzbauer, Eva Herrmann, Christoph Sarrazin, Stefan Zeuzem, Martin-Walter Welker
Immunosuppression by inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach after liver transplantation. The mTOR inhibitor sirolimus was used in selected liver graft recipients despite safety concerns and lack of approval. Everolimus is another mTOR inhibitor approved after liver transplantation. It is currently unknown, whether conversion of sirolimus to everolimus is safe in long-term liver graft recipients. Long-term liver graft recipients treated with sirolimus were converted to everolimus...
January 30, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28126553/korean-red-ginseng-improves-testicular-ineffectiveness-in-aging-rats-by-modulating-spermatogenesis-related-molecules
#13
Spandana Rajendra Kopalli, Kyu-Min Cha, Ji-Hoon Ryu, Sang-Ho Lee, Min-Sik Jeong, Seock-Yeon Hwang, Young-Joo Lee, Hee-Won Song, Su-Nam Kim, Jin-Chul Kim, Si-Kwan Kim
Korean red ginseng (Panax ginseng Meyer) is known to rejuvenate testicular effectiveness and the sperm maturation process by regulating redox proteins in aged rats. This study was performed to investigate the effect of Korean red ginseng water extract (KRG-WE) on the expression level of spermatogenesis-related key biomolecules and sex hormone receptors as well as enzymes regulating oxidation, histone deacetylation, and growth-related activities in aged rat testis. KRG-WE (200mg/kg) mixed with a regular pellet diet was administered to 12-month-old rats for 6months (KRG-AC), whereas the young (YC, 2months) and aged (AC, 12months) controls received the vehicle only...
January 23, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28122086/rapamycin-eye-drops-suppress-lacrimal-gland-inflammation-in-a-murine-model-of-sj%C3%A3-gren-s-syndrome
#14
Mihir Shah, Maria C Edman, Srikanth Reddy Janga, Frances Yarber, Zhen Meng, Wannita Klinngam, Jonathan Bushman, Tao Ma, Siyu Liu, Stan Louie, Arjun Mehta, Chuanqing Ding, J Andrew MacKay, Sarah F Hamm-Alvarez
Purpose: To evaluate the efficacy of topical rapamycin in treating autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. Methods: We developed rapamycin in a poly(ethylene glycol)-distearoyl phosphatidylethanolamine (PEG-DSPE) micelle formulation to maintain solubility. Rapamycin or PEG-DSPE eye drops (vehicle) were administered in a well-established Sjögren's syndrome disease model, the male nonobese diabetic (NOD) mice, twice daily for 12 weeks starting at 8 weeks of age...
January 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28119113/quantitative-proteomics-analysis-of-caenorhabditis-elegans-upon-germ-cell-loss
#15
Yuan-Zhu Pu, Qin-Li Wan, Ai-Jun Ding, Huai-Rong Luo, Gui-Sheng Wu
: The abrogation of the germ cells in Caenorhabditis elegans (C. elegans) by either genetic means or cell ablation results in about 60% increase of longevity. Upon the inhibition of germline stem cell proliferation, certain signaling molecules inhibit the target of rapamycin (TOR), activate the transcription factors including DAF-16, DAF-12, and PHA-4, leading to altered fatty acid lipolysis, autophagy, stress resistance, and the extended lifespan. But the exact cascades and interactions of those signaling pathways are still obscure...
March 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28116144/retraction-mechanism-of-age-related-changes-of-bone-marrow-mesenchymal-stem-cells-in-senile-osteoporosis
#16
C Huang, G F Zhang, J Han, G J Liao, B G Zou
HASH(0x4167350)
31, 2017: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28108221/sirtuin-1-independent-effects-of-resveratrol-in-ins-1e-%C3%AE-cells
#17
Cihan S Erdogan, Mathias Mørup-Lendal, Louise T Dalgaard, Ole Vang
Resveratrol (Resv), a natural polyphenol, is suggested to have various health benefits including improved insulin sensitivity. Resv activates Sirtuin (Sirt1) in several species and tissues. Sirt1 is a protein deacetylase with an important role in ageing, metabolism and β-cell function. In insulinoma β-cells (INS-1E), Resv is previously shown to improve glucose-stimulated insulin secretion in a Sirt1-dependent mechanism and to protect against β-cell dedifferentiation in non-human primates, while inducing hypertrophy in myoblasts...
February 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28104162/hypoxia-inducible-factor-1%C3%AE-expression-in-kidney-transplant-biopsy-specimens-after-reperfusion-is-associated-with-early-recovery-of-graft-function-after-cadaveric-kidney-transplantation
#18
T Oda, T Ishimura, N Yokoyama, S Ogawa, H Miyake, M Fujisaw
BACKGROUND: Ischemia/reperfusion injury during kidney transplantation (KTx) delays allograft recovery. Hypoxia-inducible factor-1α (HIF-1α) is the key regulator of the protective response to ischemia/reperfusion injury. We evaluated the impact of the HIF-1α signaling pathway on allograft recovery during cadaveric KTx. METHODS: Between 1996 and 2015, 46 patients underwent cadaveric KTx. The expression levels of HIF-1α-related proteins, including phosphoinositide 3-kinase, phosphorylated (p)-Akt, p-mammalian target of rapamycin, p-Eukaryotic translation initiation factor 4E, p-S6 ribosomal protein, and HIF-1α, were immunohistochemically evaluated and semi-quantitatively scored in graft biopsy specimens after 1 hour of revascularization...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28077803/gerosuppression-by-pan-mtor-inhibitors
#19
Olga V Leontieva, Mikhail V Blagosklonny
Rapamycin slows organismal aging and delays age-related diseases, extending lifespan in numerous species. In cells, rapamycin and other rapalogs such as everolimus suppress geroconversion from quiescence to senescence. Rapamycin inhibits some, but not all, activities of mTOR. Recently we and others demonstrated that pan-mTOR inhibitors, known also as dual mTORC1/C2 inhibitors, suppress senescent phenotype. As a continuation of these studies, here we investigated in detail a panel of pan-mTOR inhibitors, to determine their optimal gerosuppressive concentrations...
December 30, 2016: Aging
https://www.readbyqxmd.com/read/28072954/-clinical-and-immunological-analysis-of-patients-with-activated-phosphoinositide-3-kinase-%C3%AE-syndrome-resulting-from-pik3cd-mutation
#20
W J Tang, W Wang, Y Luo, Y P Wang, L Li, Y F An, L J Gou, M S Ma, T Y He, J Yang, X D Zhao, H M Song
Objective: To explore the clinical and immunological features, gene mutations, treatment and prognosis in patients with activated phosphoinositide 3-kinase δ syndrome (APDS) caused by PIK3CD gene heterozygous germline mutation. Method: The data of clinical, immunological phenotype, treatment, and prognosis of 15 patients with APDS, who visited Children's Hospital of Chongqing Medical University, Peking Union Medical College Hospital, and Shenzhen Children's Hospital from June 2014 to November 2016, were collected and analyzed...
January 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
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