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rapamycin aging

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https://www.readbyqxmd.com/read/28077803/gerosuppression-by-pan-mtor-inhibitors
#1
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
#2
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
https://www.readbyqxmd.com/read/28057021/treatment-of-intermittent-hypoxia-increases-phosphorylated-tau-in-the-hippocampus-via-biological-processes-common-to-aging
#3
Sosuke Yagishita, Seiya Suzuki, Keisuke Yoshikawa, Keiko Iida, Ayako Hirata, Masahiko Suzuki, Akihiko Takashima, Kei Maruyama, Akira Hirasawa, Takeo Awaji
Sleep-disordered breathing produces cognitive impairments, and is possibly associated with Alzheimer disease (AD). Intermittent hypoxia treatment (IHT), an experimental model for sleep-disordered breathing, results in cognitive impairments in animals via unknown mechanisms. Here, we exposed mice to IHT protocols, and performed biochemical analyses and microarray analyses regarding their hippocampal samples. In particular, we performed gene ontology (GO)-based microarray analysis to elucidate effects of IHT on hippocampal functioning, which were compared with the effects of various previously-reported experimental conditions on that (ref...
January 5, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28054657/rapamycin-prolongs-the-survival-of-corneal-epithelial-cells-in-culture
#4
Sanaz Gidfar, Farnoud Y Milani, Behrad Y Milani, Xiang Shen, Medi Eslani, Ilham Putra, Michael J Huvard, Hossein Sagha, Ali R Djalilian
Rapamycin has previously been shown to have anti-aging effects in cells and organisms. These studies were undertaken to investigate the effects of rapamycin on primary human corneal epithelial cells in vitro. Cell growth and viability were evaluated by bright field microscopy. Cell proliferation and cycle were evaluated by flow cytometry. The expression of differentiation markers was evaluated by quantitative PCR and Western blot. Senescence was evaluated by senescence-associated β-Galactosidase staining and by Western blot analysis of p16...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043938/mtorc1-activation-downregulates-fgfr3-and-pth-pthrp-receptor-in-articular-chondrocytes-to-initiate-osteoarthritis
#5
H Zhang, H Wang, C Zeng, B Yan, J Ouyang, X Liu, Q Sun, C Zhao, H Fang, J Pan, D Xie, J Yang, T Zhang, X Bai, D Cai
OBJECTIVE: Articular chondrocyte activation, involving aberrant proliferation and prehypertrophic differentiation, is essential for osteoarthritis (OA) initiation and progression. Disruption of mechanistic target of rapamycin complex 1 (mTORC1) promotes chondrocyte autophagy and survival, and decreases the severity of experimental OA. However, the role of cartilage mTORC1 activation in OA initiation is unknown. In this study, we elucidated the specific role of mTORC1 activation in OA initiation, and identify the underlying mechanisms...
December 31, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/28043164/current-treatment-options-and-investigational-drugs-for-waldenstrom-s-macroglobulinemia
#6
Maria Gavriatopoulou, Evangelos Terpos, Efstathios Kastritis, Meletios A Dimopoulos
Waldenström's Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data. Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM...
January 3, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28039705/safety-profile-of-temsirolimus-in-patients-with-metastatic-renal-cell-carcinoma
#7
Ivan Levakov, Sasa Vojinov, Goran Marusic, Milan Popov, Olivera Levakov, Mladen Popov, Dimitrije Jeremic
PURPOSE: Various targeted disease-specific therapeutics are currently approved, demonstrating a survival benefit over therapy with interferon-alpha (IFN-α) in patients with metastatic renal cell carcinoma (mRCC). Temsirolimus, a highly specific inhibitor of the mammalian target of rapamycin (mTOR), improves the overall and progression-free survival of high-risk patients with mRCC. The purpose of this study was to estimate the effects of temsirolimus on several laboratory parameters and to report the potential adverse events (AEs) in patients with mRCC...
November 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28030918/to-treat-or-not-to-treat-drug-refractory-epilepsy-by-the-ketogenic-diet-that-is-the-question
#8
REVIEW
Marzena Ułamek-Kozioł, Ryszard Pluta, Anna Bogucka-Kocka, Stanisław J Czuczwar
Epilepsy is a serious neurologic disorder worldwide which affects about 1% of the population (ca. 50 million people), the highest prevalence occurring in both children and elderly. Apart from idiopathic forms, etiology of the disease involves multiple brain risk factors - the most frequent being cerebrovascular diseases, tumours and traumatic injuries. Several treatment options exist, including, for instance, pharmacotherapy, vagal nerve stimulation or epilepsy surgery. In spite of treatment, about 30% of patients with epilepsy still have seizures and become drug-refractory...
23, 2016: Annals of Agricultural and Environmental Medicine: AAEM
https://www.readbyqxmd.com/read/28025308/2-5-dimethyl-celecoxib-extends-drosophila-life-span-via-a-mechanism-that-requires-insulin-and-target-of-rapamycin-signaling
#9
Qi Wu, Ting Lian, Xiaolan Fan, Chaochun Song, Uma Gaur, Xueping Mao, Deying Yang, Matthew D W Piper, Mingyao Yang
The search for antiaging drugs is a key component of gerontology research. A few drugs with positive effects on life span in model organisms have been found. Here, we report that 2,5-dimethyl-celecoxib, a derivative of the anti-inflammatory drug celecoxib, can extend Drosophila life span and delay aging by a mechanism involving insulin signaling and target of rapamycin signaling. Importantly, its positive effects were apparent when the treatment window was restricted to the beginning of life or the later half...
December 26, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28017716/effects-of-learning-on-mtor-pathway-gene-expression-in-the-brain-of-zebrafish-danio-rerio-of-different-ages
#10
Carolina da Silva Peixoto, Gustavo Morrone Parfitt, Gisele Eva Bruch, Marcos Freitas Cordeiro, Daniela Volcan Almeida, Luis Fernando Fernandes Marins, Daniela Martí Barros
Target of rapamycin (TOR) is a protein kinase involved in the modulation of mRNA translation and, therefore, in the regulation of protein synthesis. In neurons, the role of TOR is particularly important in the consolidation of long-term memory (LTM). One of the modulators of TOR is brain-derived neurotrophic factor (BDNF), which activates the TOR signaling pathway to promote protein synthesis, synapse strengthening, and the creation of new neural networks. We investigated the gene expression pattern of this pathway during memory consolidation in zebrafish of different ages...
December 23, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/28009055/life-history-evolution-reproduction-and-the-origins-of-sex-dependent-aging-and-longevity
#11
Robert C Brooks, Michael G Garratt
Males and females in many species differ in how they age and how long they live. These differences have motivated much research, concerning both their evolution and the underlying mechanisms that cause them. We review how differences in male and female life histories have evolved to shape patterns of aging and some of the mechanisms and pathways involved. We pay particular attention to three areas where considerable potential for synergy between mechanistic and evolutionary research exists: (1) the role of estrogens, androgens, the growth hormone/insulin-like growth factor 1 pathway, and the mechanistic target of rapamycin signaling pathway in sex-dependent growth and reproduction; (2) sexual conflict over mating rate and fertility, and how mate presence or mating can become an avenue for males and females to directly affect each other's life span; and (3) the link between dietary restriction and aging, and the emerging understanding that only the restriction of certain nutrients is involved and that this is linked to reproduction...
December 23, 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28006915/%C3%AE-dihydroagarofuran-type-sesquiterpenes-from-the-seeds-of-celastrus-monospermus-and-their-lifespan-extending-effects-on-the-nematode-caenorhabditis-elegans
#12
Lei Gao, Rujun Zhang, Jianfeng Lan, Ruonan Ning, Di Wu, Di Chen, Weimin Zhao
Seventeen β-dihydroagarofuran-type sesquiterpenes were isolated from the seeds of Celastrus monospermus, and, among them, 15 (1-15) were identified as new natural products. Nine isolates were evaluated for their lifespan-extending effect using the standard model animal nematode Caenorhabditis elegans. As a result, all of the tested compounds prolonged the lifespan of C. elegans when compared to the blank control group (p < 0.0001). Among them, celaspermin E (5) extended the average lifespan and maximum lifespan of C...
December 23, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/28005429/mammalian-target-of-rapamycin-a-target-for-lung-diseases-and-aging
#13
Brian K Kennedy, Juniper K Pennypacker
The mammalian target of rapamycin (mTOR) signaling pathway has been studied in the context of an impressive number of biological processes and disease states, including major diseases of the lung such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease, as well as the rare condition lymphangioleiomyomatosis. The involvement of mTOR in so many disease states (in and out of the lung) raises the question how one signaling pathway can have overlapping but diverse roles seemingly everywhere...
December 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27980219/overactive-mtor-signaling-leads-to-endometrial-hyperplasia-in-aged-women-and-mice
#14
Preety Bajwa, Sarah Nielsen, Janine M Lombard, Loui Rassam, Pravin Nahar, Bo R Rueda, J Erby Wilkinson, Richard A Miller, Pradeep S Tanwar
During aging, uncontrolled epithelial cell proliferation in the uterus results in endometrial hyperplasia and/or cancer development. The mTOR signaling pathway is one of the major regulators of aging as suppression of this pathway prolongs lifespan in model organisms. Genetic alterations in this pathway via mutations and/or amplifications are often encountered in endometrial cancers. However, the exact contribution of mTOR signaling and uterine aging to endometrial pathologies is currently unclear. This study examined the role of mTOR signaling in uterine aging and its implications in the development of endometrial hyperplasia...
December 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27974395/lamins-and-metabolism
#15
REVIEW
Chayki Charar, Yosef Gruenbaum
Lamins are nuclear intermediate filaments (IFs) with important roles in most nuclear activities, including nuclear organization and cell-cycle progression. Mutations in human lamins cause over 17 different diseases, termed laminopathies. Most of these diseases are autosomal dominant and can be roughly divided into four major groups: muscle diseases, peripheral neuronal diseases, accelerated aging disorders and metabolic diseases including Dunnigan type familial partial lipodystrophy (FLPD), acquired partial lipodystrophy (APL) and autosomal dominant leucodystrophy...
January 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/27960107/forebrain-depletion-of-rheb-gtpase-elicits-spatial-memory-deficits-in-mice
#16
Neelam Shahani, Wen-Chin Huang, Megan Varnum, Damon T Page, Srinivasa Subramaniam
The precise molecular and cellular events responsible for age-dependent cognitive dysfunctions remain unclear. We report that Rheb (ras homolog enriched in brain) GTPase, an activator of mammalian target of rapamycin (mTOR), regulates memory functions in mice. Conditional depletion of Rheb selectively in the forebrain of mice obtained from crossing Rheb(f/f) and CamKII(Cre) results in spontaneous signs of age-related memory loss, that is, spatial memory deficits (T-maze, Morris water maze) without affecting locomotor (open-field test), anxiety-like (elevated plus maze), or contextual fear conditioning functions...
February 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/27936094/lutein-attenuates-both-apoptosis-and-autophagy-upon-cobalt-ii-chloride-induced-hypoxia-in-rat-m%C3%A5-ller-cells
#17
Frederic K C Fung, Betty Y K Law, Amy C Y Lo
Retinal ischemia/reperfusion injury is a common feature of various retinal diseases such as glaucoma and diabetic retinopathy. Lutein, a potent anti-oxidant, is used to improve visual function in patients with age-related macular degeneration (AMD). Lutein attenuates apoptosis, oxidative stress and inflammation in animal models of acute retinal ischemia/hypoxia. Here, we further show that lutein improved Műller cell viability and enhanced cell survival upon hypoxia-induced cell death through regulation of intrinsic apoptotic pathway...
2016: PloS One
https://www.readbyqxmd.com/read/27934653/leucine-and-mammalian-target-of-rapamycin-dependent-activation-of-muscle-protein-synthesis-in-aging
#18
REVIEW
Jean-Pascal De Bandt
The preservation or restoration of muscle mass is of prime importance for healthy aging. However, aging has been repeatedly shown to be associated with resistance of muscle to the anabolic effects of feeding. Leucine supplementation has been proposed as a possible strategy because of its regulatory role on protein homeostasis. Indeed, it acts independently of growth factors and leads to enhanced cap-dependent mRNA translation initiation and increased protein synthesis. Leucine acts as a signaling molecule directly at the muscle level via the activation of mammalian/mechanistic target of rapamycin complex 1 (mTORC1)...
December 2016: Journal of Nutrition
https://www.readbyqxmd.com/read/27921039/clinical-manifestation-and-management-of-adpkd-in-western-countries
#19
REVIEW
Claudia Sommerer, Martin Zeier
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease in Western countries. The prevalence is between 2.4/10,000 and 3.9/10,000. ADPKD represents a systemic disease resulting in deterioration in renal function. Until now, mutations in two genes (PKD1 and PKD2) have been identified. Recently, the European Medicines Agency (EMA) approved the use of the vasopressin V2 receptor antagonist tolvaptan to slow the progression of cyst development and renal insufficiency connected with ADPKD in adult patients with chronic kidney disease stages 1-3 at initiation of treatment with evidence of rapidly progressing disease...
October 2016: Kidney Diseases
https://www.readbyqxmd.com/read/27921038/the-clinical-manifestation-and-management-of-autosomal-dominant-polycystic-kidney-disease-in-china
#20
REVIEW
Cheng Xue, Chen-Chen Zhou, Ming Wu, Chang-Lin Mei
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic hereditary kidney disease characterized by progressive enlargement of renal cysts. The incidence is 1-2‰ worldwide. Mutations in two genes (PKD1 and PKD2) cause ADPKD. Currently, there is no pharmaceutical treatment available for ADPKD patients in China. Summary: This review focused on advances in clinical manifestation, gene diagnosis, risk factors, and management of ADPKD in China. There is an age-dependent increase in total kidney volume (TKV) and decrease in renal function in Chinese ADPKD patients...
October 2016: Kidney Diseases
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