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Aging rapamycin

Angyang Hou, Peng Chen, He Tang, Haoye Meng, Xiaoqing Cheng, Yu Wang, Yuming Zhang, Jiang Peng
In older adults, the prevalence of osteoarthritis (OA) increases directly with age and is the most common cause of chronic disability. It is necessary to recognize that OA is a degenerative disease that strongly correlates with age, and often promotes elevated levels of cartilage injury. Chondrocytes undergo an age-dependent decline in proliferative and synthetic capacity. It is thought that cellular senescence may play a significant role in the pathology of OA, with chondrocytes exhibiting a variety of senescence-associated phenotypes...
August 11, 2018: Mechanisms of Ageing and Development
Jinlin Song, Elyse Swallow, Qayyim Said, Miranda Peeples, Mark Meiselbach, James Signorovitch, Michael Kohrman, Bruce Korf, Darcy Krueger, Michael Wong, Steven Sparagana
INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare congenital disorder often associated with epilepsy. However, real-world treatment patterns for epilepsy in patients with TSC are not yet well categorized. METHODS: This study included patients with TSC and epilepsy from fifteen clinics in the United States and one in Belgium who were enrolled in the TSC Natural History Database (2006-2014). Patient demographics and epilepsy treatment patterns, including the use of anti-epileptic drugs (AEDs), epilepsy surgeries, and dietary therapies were assessed...
August 15, 2018: Journal of the Neurological Sciences
Hannah E Walters, Lynne S Cox
Chronological age represents the greatest risk factor for many life-threatening diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing also increases susceptibility to infectious disease. Current efforts to tackle individual diseases may have little impact on the overall healthspan of older individuals, who would still be vulnerable to other age-related pathologies. However, recent progress in ageing research has highlighted the accumulation of senescent cells with chronological age as a probable underlying cause of pathological ageing...
August 8, 2018: International Journal of Molecular Sciences
Wenqiang Wei, Shaoping Ji
Cellular senescence is the arrest of normal cell division. Oncogenic genes and oxidative stress, which cause genomic DNA damage and generation of reactive oxygen species, lead to cellular senescence. The senescence-associated secretory phenotype is a distinct feature of senescence. Senescence is normally involved in the embryonic development. Senescent cells can communicate with immune cells to invoke an immune response. Senescence emerges during the aging process in several tissues and organs. In fact, increasing evidence shows that cellular senescence is implicated in aging-related diseases, such as nonalcoholic fatty liver disease, obesity and diabetes, pulmonary hypertension, and tumorigenesis...
August 5, 2018: Journal of Cellular Physiology
Michael A Liss, Lanette Rickborn, John DiGiovanni, Dean Bacich, Linda A DeGraffenried, Manish Parihar, Ian M Thompson, Zelton Dave Sharp
Prostate cancer incidence increases with age; along with many other cancers, it could be considered a disease of aging. Prostate cancer screening has led to a significant proportion of men diagnosed with low-grade, low-stage prostate cancer who are now more likely to choose an active surveillance strategy rather than definitive treatments. Definitive treatment, such as surgery and radiation therapy, is useful for high-grade disease; however, because of the low long-term risk of progression of a low-grade disease and side effects of surgery and radiation, these treatments are less commonly used for low-grade disease...
August 2018: Medical Hypotheses
Mamatha Bhat, Kristin Mara, Ross Dierkhising, Kymberly D S Watt
OBJECTIVE: To analyze immunosuppression regimens, demographic characteristics such as race, and donor features across solid organ transplant (SOT) recipients to provide better insight into their effect on the increased cancer risk in SOT. PATIENTS AND METHODS: We analyzed the Scientific Registry of Transplant Recipients database comprising 534,472 SOT recipients across the United States from October 1, 1987, through March 31, 2015. RESULTS: In total, 53,783 de novo malignancies were identified...
July 28, 2018: Mayo Clinic Proceedings
Jahahreeh Finley
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by an accelerated aging phenotype that typically leads to death via stroke or myocardial infarction at approximately 14.6 years of age. Most cases of HGPS have been linked to the extensive use of a cryptic splice donor site located in the LMNA gene due to a de novo mutation, generating a truncated and toxic protein known as progerin. Progerin accumulation in the nuclear membrane and within the nucleus distorts the nuclear architecture and negatively effects nuclear processes including DNA replication and repair, leading to accelerated cellular aging and premature senescence...
September 2018: Medical Hypotheses
Ying-Cheng Lin, Lin-Yea Horng, Hui-Ching Sung, Rong-Tsun Wu
PURPOSE: Low doses of sodium iodate (NaIO3 ) impair visual function in experimental animals with selective damage to retinal pigment epithelium (RPE) and serve as a useful model to study diseases caused by RPE degeneration. Mitochondrial dysfunction and defective autophagy have been suggested to play important roles in normal aging as well as many neurodegenerative diseases. In this study, we examined whether NaIO3 treatment disrupted the mitochondrial-lysosomal axis in cultured RPE. METHODS: The human RPE cell line, ARPE-19, was treated with low concentrations (≤500 μM) of NaIO3 ...
July 18, 2018: Journal of Ocular Pharmacology and Therapeutics
Danilo Lofaro, Anna Perri, Antonio Aversa, Benedetta Aquino, Martina Bonofiglio, Antonella La Russa, Maria Giovanna Settino, Francesca Leone, Alessandro Ilacqua, Filomena Armentano, Donatella Vizza, Simona Lupinacci, Giuseppina Toteda, Renzo Bonofiglio
BACKGROUND: Clinical studies have demonstrated that, after renal transplantation (TX), testosterone deficiency (TD) at the time of the procedure is independently associated with lower survival of the patient and graft. However, data between TD and the functional CAG polymorphism of the androgen receptor promoter (AR) are discordant. We investigated the prevalence of TD and its association with body composition, biochemical parameters, the Aging Males' Symptoms rating scale (AMS) domains and AR polymorphism...
July 17, 2018: Journal of Nephrology
Sarah J Parker, Aleksandr Stotland, Elena MacFarlane, Nicole Wilson, Amanda Orosco, Vidya Venkatraman, Kyle Madrid, Roberta A Gottlieb, Harry C Dietz, Jennifer E Van Eyk
OBJECTIVE: To (1) analyze the ascending aortic proteome within a mouse model of MFS (Fbn1C1041G/+ ) at early and late stages of aneurysm and subsequently to (2) test a novel hypothesis formulated based on this unbiased proteomic screen that links changes in integrin composition to TGFβ-dependent activation of the Rapamycin-Independent Component of TOR (Rictor) signaling pathway. Approach & Results. Ingenuity pathway analysis of over 1000 proteins quantified from in vivo MFS mouse aorta by data independent acquisition mass-spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice...
July 13, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Joan B Mannick, Melody Morris, Hans-Ulrich P Hockey, Guglielmo Roma, Martin Beibel, Kenneth Kulmatycki, Mollie Watkins, Tea Shavlakadze, Weihua Zhou, Dean Quinn, David J Glass, Lloyd B Klickstein
Inhibition of the mechanistic target of rapamycin (mTOR) protein kinase extends life span and ameliorates aging-related pathologies including declining immune function in model organisms. The objective of this phase 2a randomized, placebo-controlled clinical trial was to determine whether low-dose mTOR inhibitor therapy enhanced immune function and decreased infection rates in 264 elderly subjects given the study drugs for 6 weeks. A low-dose combination of a catalytic (BEZ235) plus an allosteric (RAD001) mTOR inhibitor that selectively inhibits target of rapamycin complex 1 (TORC1) downstream of mTOR was safe and was associated with a significant ( P = 0...
July 11, 2018: Science Translational Medicine
Han-Wei Yang, Hui-Ling Hong, Wen-Wei Luo, Chun-Mei Dai, Xin-Yi Chen, Lu-Ping Wang, Qian Li, Zi-Qing Li, Pei-Qing Liu, Zhuo-Ming Li
Vascular endothelial cell senescence is a leading cause of age-associated and vascular diseases. Mammalian target of rapamycin complex 2 (mTORC2) is a conserved serine/threonine (Ser/Thr) protein kinase that plays an important regulatory role in various cellular processes. However, its impact on endothelial senescence remains controversial. In this study we investigated the role and molecular mechanisms of mTORC2 in endothelial senescence. A replicative senescence model and H2 O2 -induced premature senescence model were established in primary cultured human umbilical vein endothelial cells (HUVECs)...
July 10, 2018: Acta Pharmacologica Sinica
Samira Shirooie, Seyed Fazel Nabavi, Ahmad R Dehpour, Tarun Belwal, Solomon Habtemariam, Sandro Argüelles, Antoni Sureda, Maria Daglia, Michał Tomczyk, Eduardo Sobarzo-Sanchez, Suowen Xu, Seyed Mohammad Nabavi
Neurodegenerative diseases (NDs) such as Parkinson's (PD), Alzheimer's (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) cause significant world-wide morbidity and mortality. To date, there is no drug of cure for these, mostly age-related diseases, although approaches in delaying the pathology and/or giving patients some symptomatic relief have been adopted for the last few decades. Various studies in recent years have shown the beneficial effects of omega-3 poly unsaturated fatty acids (PUFAs) through diverse mechanisms including anti-inflammatory effects...
July 7, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Yun Sun, Yingfeng Zheng, Chunxiao Wang, Yizhi Liu
Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells...
July 9, 2018: Cell Death & Disease
Bingbing Ma, Xiaofang He, Zhuang Lu, Lin Zhang, Jiaolong Li, Yun Jiang, Guanghong Zhou, Feng Gao
Heat stress markedly impairs the growth performance of broilers, such as the reduction of breast muscle mass and yield. The aim of this study was to examine the molecular mechanism of depressed muscle mass and yield caused by heat stress. A total of 144 (28-day-old) male broilers were allocated randomly into 3 treatment groups: (1) the normal control group (environment temperature was 22°C), (2) the heat stress group (environment temperature was 32°C), (3) the pair-fed group (environment temperature was 22°C and pair-fed to heat stress group)...
July 3, 2018: Poultry Science
György Csaba
The role of immune system is to protect the organism from the not built-in program-like alterations inside and against the agents penetrating from outside (bacteria, viruses, and protozoa). These functions were developed and formed during the evolution. Considering these functions, the immune system promotes the lengthening of lifespan and helps longevity. However, some immune functions have been conveyed by men to medical tools (e.g., pharmaceuticals, antibiotics, and prevention), especially in our modern age, which help the struggle against microbes, but evolutionarily weaken the immune system...
July 3, 2018: Acta Microbiologica et Immunologica Hungarica
Yasuo Miki, Kunikazu Tanji, Fumiaki Mori, Jun Utsumi, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
Neurodegenerative disorders such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are characterized by impairment of autophagy. Cellular survival is dependent on efficient clearance of phosphorylated α-synuclein, which accumulates as fibrils in the neuronal cytoplasm as Lewy bodies (LBs). The forkhead box O 1 (FOXO1) is a member of the FOXO family that functions in various intracellular processes including regulation of autophagy. Transcriptional activation of FOXO1 has been reported to initiate autophagy by inhibiting the expression of Mechanistic Target of Rapamycin (mTOR), mediated by sestrin 3 (SESN3) and tuberous sclerosis complex 2 (TSC2)...
June 30, 2018: Neuroscience Letters
Martina Gáliková, Peter Klepsatel
Being overweight increases the risk of many metabolic disorders, but how it affects lifespan is not completely clear. Not all obese people become ill, and the exact mechanism that turns excessive fat storage into a health-threatening state remains unknown. Drosophila melanogaster has served as an excellent model for many diseases, including obesity, diabetes, and hyperglycemia-associated disorders, such as cardiomyopathy or nephropathy. Here, we review the connections between fat storage and aging in different types of fly obesity...
June 27, 2018: International Journal of Molecular Sciences
Nina Gubina, Alba Naudi, Rhoda Stefanatos, Mariona Jove, Filippo Scialo, Daniel J Fernandez-Ayala, Tommi Rantapero, Ihor Yurkevych, Manuel Portero-Otin, Matti Nykter, Oleh Lushchak, Placido Navas, Reinald Pamplona, Alberto Sanz
Aging is a multifactorial process which affects all animals. Aging as a result of damage accumulation is the most accepted explanation but the proximal causes remain to be elucidated. There is also evidence indicating that aging has an important genetic component. Animal species age at different rates and specific signalling pathways, such as insulin/insulin-like growth factor, can regulate lifespan of individuals within a species by reprogramming cells in response to environmental changes. Here, we use an unbiased approach to identify novel factors that regulate lifespan in Drosophila melanogaster...
June 26, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Abhishek Kumar Singh, Sandeep Singh, Vinay Kumar Tripathi, Akalabya Bissoyi, Geetika Garg, Syed Ibrahim Rizvi
Brain aging is an intricate and natural phenomenon exclusively characterized by oxidative stress, accumulation of oxidatively damaged macromolecules, and alterations in structure and function of neurons that further increase the risk factor for most of the neurodegenerative diseases. In addition, age-dependent defective autophagy has also been implicated to favour the pathogenesis and prevalence of the neurological diseases. Therefore, the development of strategies that delay aging and the concomitant neurological disorders remain elusive...
June 26, 2018: Rejuvenation Research
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