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Aging rapamycin

Lihua Yao, Mingyang Li, Jingwen Hu, Wangsheng Wang, Minzhi Gao
Polycystic ovary syndrome (PCOS) is a major cause of infertility in women of reproductive age. However, its exact etiology remains unknown. In this study, we sequenced miRNAs in human follicular fluid and identified 16 downregulated and 3 upregulated miRNAs in PCOS group compared with non-PCOS group. Among the differential expressed miRNAs, miR-335-5p was verified lower abundance in PCOS than non-PCOS group using quantitative real-time PCR. Besides, miR-335-5p negatively correlated with antral follicle count, anti-Müllerian hormone and total testosterone...
September 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Verónica Ruiz-Torres, Maria Losada-Echeberría, Maria Herranz-López, Enrique Barrajón-Catalán, Vicente Galiano, Vicente Micol, José Antonio Encinar
Mammalian target of rapamycin (mTOR) is a PI3K-related serine/threonine protein kinase that functions as a master regulator of cellular growth and metabolism, in response to nutrient and hormonal stimuli. mTOR functions in two distinct complexes-mTORC1 is sensitive to rapamycin, while, mTORC2 is insensitive to this drug. Deregulation of mTOR's enzymatic activity has roles in cancer, obesity, and aging. Rapamycin and its chemical derivatives are the only drugs that inhibit the hyperactivity of mTOR, but numerous side effects have been described due to its therapeutic use...
October 15, 2018: Marine Drugs
Malcolm Pyles Chelliah, Huy M Do, Zachary Zinn, Viraat Patel, Michael Jeng, Rohit K Khosla, Mai-Thy Truong, Ann Marqueling, Joyce M C Teng
Importance: Current therapeutic options for patients with extracranial head and neck arteriovenous malformations are limited. Surgical intervention, such as sclerotherapy or resection, often result in rapid recurrence and progression of disease. Objective: To assess the efficacy and tolerability of sirolimus as an adjuvant therapy for endovascular embolization in the management of complicated extracranial head and neck arteriovenous malformations. Design, Setting, and Participants: This case series examined 6 patients with extracranial head and neck arteriovenous malformations treated from January 1, 2013, to December 31, 2017, at a multidisciplinary vascular anomalies clinic within Stanford Hospital and Clinics...
September 19, 2018: JAMA Dermatology
Hak Joo Lee, Olga Gonzalez, Edward J Dick, Andrew Donati, Denis Feliers, Choudhury Goutam Ghosh, Corinna Ross, Manjeri Venkatachalam, Suzette D Tardif, Balakuntalam S Kasinath
We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes...
October 13, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Nathanael Matei, Richard Camara, John H Zhang
Clinical and pre-clinical studies have reported a broad range of applications for hydrogen gas therapy. Classically, conventional antioxidant therapy is limited because it neutralizes both the detrimental and protective effects of reactive oxygen species. As a weak reducing agent, hydrogen gas avoids this paradox by reacting with strong oxidants while leaving other beneficial oxidants reactive. This review gathers a promising list of hydrogen gas applications that merit further mechanistic investigation and additional therapeutic trials...
July 2018: Medical Gas Research
T Ueno, S Hiwatashi, R Saka, H Yamanaka, Y Takama, Y Tazuke, K Bessho, H Okuyama
Chronic rejection (CR) remains a challenging complication after liver transplantation. Everolimus, which is a mammalian target of rapamycin inhibitor, has an anti-fibrosis effect. We report here the effect of everolimus on CR. Case 1 was a 7-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 10 months of age. Liver function tests (LFTs) did not improve after transplantation despite treatment with tacrolimus + mycophenolate mofetil (MMF). Antithymoglobulin (ATG) and steroid pulse therapy were also ineffective...
March 19, 2018: Transplantation Proceedings
Thiago R Araujo, Joel A da Silva, Jean F Vettorazzi, Israelle N Freitas, Camila Lubaczeuski, Emily A Magalhães, Juliana N Silva, Elane S Ribeiro, Antonio C Boschero, Everardo M Carneiro, Maria L Bonfleur, Rosane Aparecida Ribeiro
Obesity predisposes to glucose intolerance and type 2 diabetes (T2D). This disease is often characterized by insulin resistance, changes in insulin clearance, and β-cell dysfunction. However, studies indicate that, for T2D development, disruptions in glucagon physiology also occur. Herein, we investigated the involvement of glucagon in impaired glycemia control in monosodium glutamate (MSG)-obese mice. Male Swiss mice were subcutaneously injected daily, during the first 5 days after birth, with MSG (4 mg/g body weight [BW]) or saline (1...
October 14, 2018: Journal of Cellular Physiology
Aubrey M Sills, Joselyn M Artavia, Brian D DeRosa, Corinna N Ross, Adam B Salmon
Interventions to extend lifespan and improve health with increasing age would have significant impact on a growing aged population. There are now several pharmaceutical interventions that extend lifespan in laboratory rodent models with rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) being the most well studied. In this study, we report on the hematological effects in a cohort of middle-aged common marmosets (Callithrix jacchus) that were enrolled in a study to test the effects of daily rapamycin treatment on aging in this species...
October 12, 2018: American Journal of Primatology
Dudley W Lamming, Liron Bar-Peled
For the past five decades the lysosome has been characterized as an unglamorous cellular recycling center. This notion has undergone a radical shift in the last ten years, with new research revealing that this organelle serves as a major hub for metabolic signaling pathways. The discovery that master growth regulators, including the protein kinase mTOR (mechanistic Target Of Rapamycin) make their home at lysosomal surface has generated intense interest in the lysosome's key role in nutrient sensing and cellular homeostasis...
October 10, 2018: Traffic
Sarah Löw, Catherine H Han, Tracy T Batchelor
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL), confined to the brain, eyes, spinal cord or leptomeninges without systemic involvement. Overall prognosis, diagnosis and management of PCNSL differ from other types of NHL. Prompt diagnosis and initiation of treatment are vital to improving clinical outcomes. PCNSL is responsive to radiation therapy, however whole-brain radiotherapy (WBRT) inadequately controls the disease when used alone and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients...
2018: Therapeutic Advances in Neurological Disorders
Mehmet Canpolat, Hakan Gumus, Sefer Kumandas, Abdulhakim Coskun, Huseyin Per
PURPOSE: The purpose of this study was to evaluate the long-term results of eight cases diagnosed with tuberous sclerosis complex (TSC) and receiving rapamycin therapy because of epileptic seizures and/or accompanying TSC findings. METHOD: Rapamycin therapy was initiated at a dose of 1.5 mg/m2 . Seizure frequency, electroencephalographic (EEG) findings, renal and cranial imaging findings, and cutaneous lesions over 3- to 6-month periods during follow-up and treatment were evaluated...
October 7, 2018: Epilepsy & Behavior: E&B
Pablo García Montero, Javier Del Boz, Eulalia Baselga Torres, José Manuel Azaña Defez, Manuel Alcaraz Vera, Jesús Tercedor Sánchez, Lucero Noguera Morel, Ángel Vera Casaño
BACKGROUND: The superficial lymphatic component of vascular malformations poses a significant treatment challenge. It is responsible for the majority of symptoms presented and to date there is no consensus regarding treatment. OBJECTIVE: To evaluate the effectiveness of topical rapamycin in treating superficial lymphatic malformations (LM). METHODS: A case series study was performed of patients with superficial LM, treated with topical rapamycin...
October 5, 2018: Journal of the American Academy of Dermatology
György Csaba
The human lifespan in the developed countries significantly increased, from about 40 years to 80 years, in the last hundred years. This change is due to multiple factors, however, the development of medicine and pharmacological research as well as social well-being and social care are primarily important. For aging, the attrition of the parts of the whole organism are responsible, which is caused by endogenous oxidation processes (free radicals), which can destroy any cells in the organism. The injury of the defense or regulatory organ systems (immune system, neuroendocrine system) influences the whole organism, causing its decline (aging), later complete loss of abilities (death)...
October 2018: Orvosi Hetilap
Sam Amin, Andrew Lux, Finbar O'Callaghan
Our knowledge of the effect of metformin on human health is increasing. In addition to its ability to improve the control of hyperglycaemia, metformin has been shown to reduce the burden of ageing via effects on damaged DNA and the process of apoptosis. Studies have shown that metformin may reduce the risk of cardiovascular disease through influences on body weight, blood pressure, cholesterol levels and the progression of atherosclerosis. Studies also suggest that metformin may be beneficial for neuro-psychiatric disorders, cognitive impairment and in reducing the risk of dementia, erectile dysfunction and Duchenne Muscular Dystrophy...
October 5, 2018: British Journal of Clinical Pharmacology
Shameena Bake, Andre Okoreeh, Homa Khosravian, Farida Sohrabji
Our previous studies showed that Insulin-like Growth Factor (IGF)-1 reduced blood brain barrier pemeability and decreased infarct volume caused by middle cerebral artery occlusion (MCAo) in middle aged female rats. Similarly, cultures of primary brain microvessel endothelial cells from middle-aged female rats and exposed to stroke-like conditions (oxygen glucose deprivation; OGD) confirmed that IGF-1 reduced dye transfer across this cell monolayer. Surprisingly, IGF-1 did not attenuate endothelial cell death caused by OGD...
October 1, 2018: Experimental Neurology
J J McCormick, T A VanDusseldorp, C G Ulrich, R L Lanphere, K Dokladny, P L Mosely, C M Mermier
Autophagy is a lysosome degradation pathway through which damaged organelles and macromolecules are degraded within the cell. A decrease in activity of the autophagic process has been linked to several age-associated pathologies, including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction. Here, we examined the differences in the autophagic response using autophagy-inducer rapamycin (Rapa) in peripheral blood mononuclear cells (PBMCs) from young (21.8 ± 1...
September 1, 2018: Physiology International
Jae-Hong Jeong, Mi-Bo Kim, Changhee Kim, Jae-Kwan Hwang
Vitamin C significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity, with both the suppression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulation of cell-cycle activators (E2F1 and E2F2). Vitamin C also effectively attenuated the hyperactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase-B (AKT) signaling pathway. The expression of the longevity marker, the mammalian target of rapamycin (mTOR), was down-regulated by vitamin C while the expressions of forkhead box O3a (FoxO3a) and sirtuin1 (SIRT1) were up-regulated by vitamin C...
April 2018: Food Science and Biotechnology
Zhijing Zhao, Junfeng Ma, Ying Mao, Liying Dong, Siqi Li, Yi Zhang
BACKGROUND α1-antitrypsin (α1-AT) is highly expressed in many tumors. However, to the best of our knowledge, its relationship to triple negative breast cancer (TNBC) has not yet been studied. Thus, in this research we first explored the influence of α1-AT silencing on the abilities of migration and invasion, and then further study its molecular mechanism in TNBC cells. MATERIAL AND METHODS The viability of MDA-MB-231 cells were detected using cell counting kit-8 (CCK-8). The abilities of migration and invasion were examined by Transwell assay...
September 27, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Mohammed S Abdel-Maksoud, Mohammed I El-Gamal, Dalia Reyane Benhalilou, Sandy Ashraf, Shatha Abdulghaffar Mohammed, Chang-Hyun Oh
The mechanistic/mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin, regulates many normal cell processes such as transcription, cell growth, and autophagy. Overstimulation of mTOR by its ligands, amino acids, sugars, and/or growth factors leads to physiological disorders, including cancer and neurodegenerative diseases. In this study, we reviewed the recent advances regarding the mechanism that involves mTOR in cancer, aging, and neurodegenerative diseases. The chemical and biological properties of recently reported small molecules that function as mTOR kinase inhibitors, including adenosine triphosphate-competitive inhibitors and dual mTOR/PI3K inhibitors, have also been reviewed...
September 24, 2018: Medicinal Research Reviews
Xiaolong Fu, Xiaoyang Sun, Linqing Zhang, Yecheng Jin, Renjie Chai, Lili Yang, Aizhen Zhang, Xiangguo Liu, Xiaochun Bai, Jianfeng Li, Haibo Wang, Jiangang Gao
The underlying molecular mechanisms of age-related hearing loss (ARHL) in humans and many strains of mice have not been fully characterized. This common age-related disorder is assumed to be closely associated with oxidative stress. Here, we demonstrate that mTORC1 signaling is highly and specifically activated in the cochlear neurosensory epithelium (NSE) in aging mice, and rapamycin injection prevents ARHL. To further examine the specific role of mTORC1 signaling in ARHL, we generated murine models with NSE-specific deletions of Raptor or Tsc1, regulators of mTORC1 signaling...
September 24, 2018: Journal of Clinical Investigation
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