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rapamycin aging

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https://www.readbyqxmd.com/read/29779024/a-randomized-clinical-trial-of-metformin-to-treat-autosomal-dominant-polycystic-kidney-disease
#1
Stephen L Seliger, Kaleab Z Abebe, Kenneth R Hallows, Dana C Miskulin, Ronald D Perrone, Terry Watnick, Kyongtae Tae Bae
BACKGROUND: Metformin inhibits cyclic AMP generation and activates AMP-activated protein kinase (AMPK), which inhibits the cystic fibrosis transmembrane conductance regulator and Mammalian Target of Rapamycin pathways. Together these effects may reduce cyst growth in autosomal dominant polycystic kidney disease (ADPKD). METHODS: A phase II, double-blinded randomized placebo-controlled trial of 26 months duration. Participants will include nondiabetic adults (n = 96) aged 18-60 years, with an estimated glomerular filtration rate (eGFR) ≥50 mL/min/1...
May 18, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29779018/common-and-unique-transcriptional-responses-to-dietary-restriction-and-loss-of-insulin-receptor-substrate-1-irs1-in-mice
#2
Melissa M Page, Eugene F Schuster, Manikhandan Mudaliar, Pawel Herzyk, Dominic J Withers, Colin Selman
Dietary restriction (DR) is the most widely studied non-genetic intervention capable of extending lifespan across multiple taxa. Modulation of genes, primarily within the insulin/insulin-like growth factor signalling (IIS) and the mechanistic target of rapamycin (mTOR) signalling pathways also act to extend lifespan in model organisms. For example, mice lacking insulin receptor substrate-1 (IRS1) are long-lived and protected against several age-associated pathologies. However, it remains unclear how these particular interventions act mechanistically to produce their beneficial effects...
May 20, 2018: Aging
https://www.readbyqxmd.com/read/29778908/mammalian-target-of-rapamycin-complex-2-signaling-in-obese-women-changes-after-bariatric-surgery
#3
Marcela Augusta de Souza Pinhel, Carolina Ferreira Nicoletti, Natalia Yumi Noronha, Bruno Affonso Parenti de Oliveira, Cristiana Cortes-Oliveira, Wilson Salgado, Wilson Araujo da Silva, Doroteia Rossi Silva Souza, Julio Sergio Marchini, Carla Barbosa Nonino
OBJECTIVES: After bariatric surgery, modifications to signaling pathway networks including those of the metabolic regulator called mammalian or mechanistic target of rapamycin (mTOR) may lead to molecular alterations related to energy source availability, systemic nutrients, and catabolic and anabolic cellular processes. This study aimed to identify gene expression changes with regard to the mTOR complex 2 subunit signaling pathway in obese patients before and after bariatric surgery...
March 21, 2018: Nutrition
https://www.readbyqxmd.com/read/29774169/phase-2-study-of-everolimus-for-relapsed-or-refractory-classical-hodgkin-lymphoma
#4
Patrick B Johnston, Lauren C Pinter-Brown, Ghulam Warsi, Kristen White, Radhakrishnan Ramchandren
Background: The current standard of care for classical Hodgkin lymphoma (HL) is multiagent chemotherapy with or without radiation. In patients who relapse or fail to respond, additional high-dose chemotherapy with autologous hematopoietic stem cell transplantation (AHSCT) can improve progression-free survival (PFS). Novel therapies are required for patients refractory to chemotherapy and AHSCT. The mammalian target of rapamycin inhibitor everolimus has shown preliminary activity in preclinical models of HL and promising efficacy in patients with relapsed or refractory HL...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29769719/klhl22-activates-amino-acid-dependent-mtorc1-signalling-to-promote-tumorigenesis-and-ageing
#5
Jie Chen, Yuhui Ou, Yanyan Yang, Wen Li, Ye Xu, Yuntao Xie, Ying Liu
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2 . Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4 . In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6 . The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 ...
May 16, 2018: Nature
https://www.readbyqxmd.com/read/29762821/the-influencing-mechanism-of-mtor-signal-pathway-mediated-by-mitofusin-2-in-development-of-follicle
#6
Q-Y Luo, P Huo, L-L Wang, X-H Wu
OBJECTIVE: To investigate the influencing mechanism of mammalian target of rapamycin (mTOR) signal pathway mediated by mitofusin-2 (Mfn2) in the development of follicle. MATERIALS AND METHODS: We selected 20 healthy Sprague Dawley (SD) female rats aging between 6 and 8 weeks were divided into the control group and the polycystic ovarian syndrome (PCOS) model group. Rats in PCOS group received the lavage using 0.4 mL 1% carboxymethyl cellulose solution containing letrozole (1 mg/kg/d) consecutively for 20 to 25d...
April 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29757673/rapamycin-insensitive-mechanistic-target-of-rapamycin-regulates-basal-and-resistance-exercise-induced-muscle-protein-synthesis
#7
Riki Ogasawara, Takeshi Suginohara
We investigated whether rapamycin-insensitive mechanistic target of rapamycin (mTOR) signaling plays a role in regulating resistance exercise-induced muscle protein synthesis. We used a rodent model of resistance exercise and compared the effect of rapamycin, an allosteric mTOR inhibitor, with the effect of AZD8055, an ATP-competitive mTOR kinase inhibitor. The right gastrocnemius muscle of male Sprague-Dawley rats age 11 wk was contracted isometrically via percutaneous electrical stimulation (100 Hz, 5 sets of ten 3-s contractions, 7 s of rest between contractions, 3 min of rest between sets), and the left gastrocnemius muscle served as control...
May 14, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29753771/mir-199a-3p-regulates-brown-adipocyte-differentiation-through-mtor-signaling-pathway
#8
Yao Gao, Yan Cao, Xianwei Cui, Xingyun Wang, Yahui Zhou, Fangyan Huang, Xing Wang, Juan Wen, Kaipeng Xie, Pengfei Xu, Xirong Guo, Lianghui You, Chenbo Ji
Recent discoveries of functional brown adipocytes in mammals illuminates their therapeutic potential for combating obesity and its associated diseases. However, on account of the limited amount and activity in adult humans of brown adipocyte depots, identification of miRNAs and characterization their regulatory roles in human brown adipogenesis are urgently needed. This study focused on the role of microRNA (miR)-199a-3p in human brown adipocyte differentiation and thermogenic capacity. A decreased expression pattern of miR-199a-3p was consistently observed during the differentiation course of brown adipocytes in mice and humans...
May 10, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29752839/the-role-of-mtor-in-ovarian-cancer-polycystic-ovary-syndrome-and-ovarian-aging
#9
REVIEW
Jin Liu, Dai-Chao Wu, Li-Hua Qu, Hong-Qing Liao, Mei-Xiang Li
The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions...
May 12, 2018: Clinical Anatomy
https://www.readbyqxmd.com/read/29752013/-lymphedema-in-patients-treated-with-sirolimus-15-cases
#10
C Fourgeaud, L Simon, B Benoughidane, S Vignes
BACKGROUND: Sirolimus is a mammalian target of rapamycin (mTOR) inhibitor used after organ transplantation and to treat vascular malformations. Among its adverse effects, limb lymphedema has been described. OBJECTIVE: The aim of this study was to analyze the clinical features, lymphoscintigraphy and lymphedema outcome in patients treated with sirolimus. PATIENTS AND METHODS: Monocentric retrospective study from January 2008 to September 2017 analyzing all consecutive patients having lymphedema occurring with sirolimus...
May 8, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29751091/sestrins-are-differentially-expressed-with-age-in-the-skeletal-muscle-of-men-a-cross-sectional-analysis
#11
Nina Zeng, Randall F D'Souza, Cameron J Mitchell, David Cameron-Smith
A gradual loss of skeletal muscle mass is a common feature of aging, leading to impaired insulin sensitivity and mobility. Sestrin1, 2, 3 are multifunctional proteins that regulate the mammalian target of rapamycin complex (mTORC1), autophagy and redox homeostasis. It is unclear how aging affects Sestrins and their downstream targets in human, therefore this study examined the basal expression of Sestrins in three age groups, young, middle-aged and older men and explored the mTORC1 pathway, autophagy markers and antioxidant regulation...
May 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29747425/glucosamine-induced-autophagy-through-ampk%C3%A2-mtor-pathway-attenuates-lipofuscin-like-autofluorescence-in-human-retinal-pigment-epithelial-cells-in-vitro
#12
Ching-Long Chen, Yi-Hao Chen, Chang-Min Liang, Ming-Cheng Tai, Da-Wen Lu, Jiann-Torng Chen
Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29745797/reversing-age-associated-arterial-dysfunction-insight-from-preclinical-models
#13
Venkateswara Reddy Gogulamudi, Jinjin Cai, Lisa A Lesniewski
Cardiovascular diseases (CVDs) remain the leading causes of death in the US, and advancing age is a primary risk factor. Impaired endothelium dependent dilation and increased stiffening of the arteries with aging are independent predictors of CVD. Increased tissue and systemic oxidative stress and inflammation underlie this age-associated arterial dysfunction. Calorie restriction (CR) is the most powerful intervention known to increase lifespan and improve age-related phenotypes, including arterial dysfunction...
May 10, 2018: Journal of Applied Physiology
https://www.readbyqxmd.com/read/29729230/role-of-hypothalamus-in-aging-and-its-underlying-cellular-mechanisms
#14
REVIEW
Keetae Kim, Han Kyoung Choe
Aging is characterized by a progressive loss of several physiological functions that can cause various age-related disorders. Several factors have been identified as causes of aging to elucidate the decline in functions. Various aspects of physiological deterioration are controlled by the hypothalamus, a critical brain region that connects the neuroendocrine system to physiological functions. In addition, functional alterations in a set of agouti-related peptide/neuropeptide Y (AgRP/NPY) and pro-opiomelanocortin (POMC) neurons, a set of growth hormone-releasing hormone (GHRH) and somatostatin (SST) neurons, a set of arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) neurons, and a set of gonadotropin-releasing hormone (GnRH) and kisspeptin/neurokinin B/dynorphin (KNDy) neurons contribute to age-related physiological decline in energy metabolism, hormone regulation, circadian rhythm, and reproduction, respectively...
May 2, 2018: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/29708496/reduced-expression-of-c-ebp%C3%AE-lip-extends-health-and-lifespan-in-mice
#15
Christine Müller, Laura M Zidek, Tobias Ackermann, Tristan de Jong, Peng Liu, Verena Kliche, Mohamad Amr Zaini, Gertrud Kortman, Liesbeth Harkema, Dineke S Verbeek, Jan P Tuckermann, Julia von Maltzahn, Alain de Bruin, Victor Guryev, Zhao-Qi Wang, Cornelis F Calkhoven
Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb -mRNA. Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice...
April 30, 2018: ELife
https://www.readbyqxmd.com/read/29705807/rapamycin-protects-skin-fibroblasts-from-ultraviolet-b-induced-photoaging-by-suppressing-the-production-of-reactive-oxygen-species
#16
Dengke Qin, Runjian Ren, Chuanlong Jia, Yongzhou Lu, Qingjian Yang, Liang Chen, Xinyuan Wu, Jingjing Zhu, Yu Guo, Ping Yang, Yiqun Zhou, Ningwen Zhu, Bo Bi, Tianyi Liu
BACKGROUND/AIMS: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29702558/a-low-protein-diet-for-diabetic-kidney-disease-its-effect-and-molecular-mechanism-an-approach-from-animal-studies
#17
REVIEW
Munehiro Kitada, Yoshio Ogura, Itaru Monno, Daisuke Koya
A low-protein diet (LPD) can be expected to retard renal function decline in advanced stages of chronic kidney disease (CKD), including diabetic kidney disease (DKD), and is recommended in a clinical setting. Regarding the molecular mechanisms of an LPD against DKD, previous animal studies have shown that an LPD exerts reno-protection through mainly the improvement of glomerular hyperfiltration/hypertension due to the reduction of intraglomerular pressure. On the other hand, we have demonstrated that an LPD, particularly a very-LPD (VLPD), improved tubulo-interstitial damage, inflammation and fibrosis, through the restoration of autophagy via the reduction of a mammalian target of rapamycin complex 1 (mTORC1) activity in type 2 diabetes and obesity animal models...
April 27, 2018: Nutrients
https://www.readbyqxmd.com/read/29697822/renal-angiomyolipoma-in-patients-with-tuberous-sclerosis-complex-findings-from-the-tuberous-sclerosis-registry-to-increase-disease-awareness
#18
J Chris Kingswood, Elena Belousova, Mirjana P Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, Lisa D' Amato, Guillaume Beaure d'Augères, Petrus J de Vries, José C Ferreira, Martha Feucht, Carla Fladrowski, Christoph Hertzberg, Sergiusz Jozwiak, John A Lawson, Alfons Macaya, Ruben Marques, Rima Nabbout, Finbar O'Callaghan, Jiong Qin, Valentin Sander, Matthias Sauter, Seema Shah, Yukitoshi Takahashi, Renaud Touraine, Sotiris Youroukos, Bernard Zonnenberg, Anna C Jansen
Background: Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with an aim to provide detailed clinical characteristics of renal angiomyolipoma among patients with TSC...
April 25, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29691711/biomechanics-and-mechanical-signaling-in-the-ovary-a-systematic-review
#19
REVIEW
Jaimin S Shah, Reem Sabouni, Kamaria C Cayton Vaught, Carter M Owen, David F Albertini, James H Segars
PURPOSE: Mammalian oogenesis and folliculogenesis share a dynamic connection that is critical for gamete development. For maintenance of quiescence or follicular activation, follicles must respond to soluble signals (growth factors and hormones) and physical stresses, including mechanical forces and osmotic shifts. Likewise, mechanical processes are involved in cortical tension and cell polarity in oocytes. Our objective was to examine the contribution and influence of biomechanical signaling in female mammalian gametogenesis...
April 24, 2018: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/29689132/alcohol-delays-the-onset-of-puberty-in-the-female-rat-by-altering-key-hypothalamic-events
#20
Vinod K Srivastava, Jill K Hiney, William L Dees
BACKGROUND: Because alcohol (ALC) delays signs of pubertal development, we assessed the time course of events associated with the synthesis of critical hypothalamic peptides that regulate secretion of luteinizing hormone-releasing hormone (LHRH), the peptide that drives the pubertal process. METHODS: Immature female rats were administered either lab chow or Bio-Serve isocaloric control or ALC liquid diets from 27 through 33 days of age. On days 28, 29, 31 and 33 animals were killed by decapitation and tissue blocks containing the medial basal hypothalamus (MBH) and the rostral hypothalamic area (RHA) were isolated and stored frozen until assessed by Western blot analysis...
April 24, 2018: Alcoholism, Clinical and Experimental Research
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