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Rafael de Cabo

Camila Quartim de Moraes Bruna, Rafael Queiroz de Souza, Irineu Francisco Silva Massaia, Áurea Silveira Cruz, Kazuko Uchikawa Graziano
Objectives: to determine if there are differences on the safety of the preparation of clean surgical instruments using different types of gloves and bare hands and evaluate the microbiological load of these preparations without gloves. Method: laboratory procedure with a pragmatic approach, in which the samples were handled with different types of gloves and bare hands. In addition, cytotoxicity assays were carried out by means of the agar diffusion method. Further samples were subjected to microbiological analysis after being handled without gloves...
October 10, 2016: Revista Latino-americana de Enfermagem
Serra Ucer, Srividhya Iyer, Ha-Neui Kim, Li Han, Christine Rutlen, Kelly Allison, Jeff D Thostenson, Rafael de Cabo, Robert L Jilka, Charles O'Brien, Maria Almeida, Stavros C Manolagas
Old age and sex steroid deficiency are the two most critical factors for the development of osteoporosis. It remains unknown, however, whether the molecular culprits of the two conditions are similar or distinct. We show herein that at 19.5 months of age - a time by which the age-dependent decline of cortical and cancellous bone mass and cortical porosity were fully manifested in C57BL/6J mice - these animals remained functionally estrogen sufficient. Transgenic mice with conditional expression of mitochondria-targeted catalase - a potent H2 O2 inactivating enzyme - in cells of the myeloid lineage (mitoCAT;LysM-Cre mice), were protected from the loss of cortical, but not cancellous, bone caused by gonadectomy in either sex...
October 7, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Andrea Di Francesco, Clara Di Germanio, Amaresh C Panda, Phu Huynh, Robert Peaden, Ignacio Navas-Enamorado, Paul Bastian, Elin Lehrmann, Alberto Diaz-Ruiz, David Ross, David Siegel, Jennifer L Martindale, Michel Bernier, Myriam Gorospe, Kotb Abdelmohsen, Rafael de Cabo
NAD(P)H: quinone oxidoreductase (NQO1) is essential for cell defense against reactive oxidative species, cancer, and metabolic stress. Recently, NQO1 was found in ribonucleoprotein (RNP) complexes, but NQO1-interacting mRNAs and the functional impact of such interactions are not known. Here, we used ribonucleoprotein immunoprecipitation (RIP) and microarray analysis to identify comprehensively the subset of NQO1 target mRNAs in human hepatoma HepG2 cells. One of its main targets, SERPINA1 mRNA, encodes the serine protease inhibitor α-1-antitrypsin, A1AT, which is associated with disorders including obesity-related metabolic inflammation, chronic obstructive pulmonary disease (COPD), liver cirrhosis and hepatocellular carcinoma...
August 8, 2016: Free Radical Biology & Medicine
Stefano Di Biase, Changhan Lee, Sebastian Brandhorst, Brianna Manes, Roberta Buono, Chia-Wei Cheng, Mafalda Cacciottolo, Alejandro Martin-Montalvo, Rafael de Cabo, Min Wei, Todd E Morgan, Valter D Longo
Immune-based interventions are promising strategies to achieve long-term cancer-free survival. Fasting was previously shown to differentially sensitize tumors to chemotherapy while protecting normal cells, including hematopoietic stem and immune cells, from its toxic side effects. Here, we show that the combination of chemotherapy and a fasting-mimicking diet (FMD) increases the levels of bone marrow common lymphoid progenitor cells and cytotoxic CD8(+) tumor-infiltrating lymphocytes (TILs), leading to a major delay in breast cancer and melanoma progression...
July 11, 2016: Cancer Cell
Devin Wahl, Victoria C Cogger, Samantha M Solon-Biet, Rosilene V R Waern, Rahul Gokarn, Tamara Pulpitel, Rafael de Cabo, Mark P Mattson, David Raubenheimer, Stephen J Simpson, David G Le Couteur
Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans...
November 2016: Ageing Research Reviews
Sarah J Mitchell, Julio Madrigal-Matute, Morten Scheibye-Knudsen, Evandro Fang, Miguel Aon, José A González-Reyes, Sonia Cortassa, Susmita Kaushik, Marta Gonzalez-Freire, Bindi Patel, Devin Wahl, Ahmed Ali, Miguel Calvo-Rubio, María I Burón, Vincent Guiterrez, Theresa M Ward, Hector H Palacios, Huan Cai, David W Frederick, Christopher Hine, Filomena Broeskamp, Lukas Habering, John Dawson, T Mark Beasley, Junxiang Wan, Yuji Ikeno, Gene Hubbard, Kevin G Becker, Yongqing Zhang, Vilhelm A Bohr, Dan L Longo, Placido Navas, Luigi Ferrucci, David A Sinclair, Pinchas Cohen, Josephine M Egan, James R Mitchell, Joseph A Baur, David B Allison, R Michael Anson, José M Villalba, Frank Madeo, Ana Maria Cuervo, Kevin J Pearson, Donald K Ingram, Michel Bernier, Rafael de Cabo
Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria...
June 14, 2016: Cell Metabolism
Paula Mera, Kathrin Laue, Mathieu Ferron, Cyril Confavreux, Jianwen Wei, Marta Galán-Díez, Alain Lacampagne, Sarah J Mitchell, Julie A Mattison, Yun Chen, Justine Bacchetta, Pawel Szulc, Richard N Kitsis, Rafael de Cabo, Richard A Friedman, Christopher Torsitano, Timothy E McGraw, Michelle Puchowicz, Irwin Kurland, Gerard Karsenty
Circulating levels of undercarboxylated and bioactive osteocalcin double during aerobic exercise at the time levels of insulin decrease. In contrast, circulating levels of osteocalcin plummet early during adulthood in mice, monkeys, and humans of both genders. Exploring these observations revealed that osteocalcin signaling in myofibers is necessary for adaptation to exercise by favoring uptake and catabolism of glucose and fatty acids, the main nutrients of myofibers. Osteocalcin signaling in myofibers also accounts for most of the exercise-induced release of interleukin-6, a myokine that promotes adaptation to exercise in part by driving the generation of bioactive osteocalcin...
June 14, 2016: Cell Metabolism
Clara Di Germanio, Michel Bernier, Michael Petr, Mauro Mattioli, Barbara Barboni, Rafael de Cabo
Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage...
May 29, 2016: Oncotarget
Ji Heon Noh, Kyoung Mi Kim, Kotb Abdelmohsen, Je-Hyun Yoon, Amaresh C Panda, Rachel Munk, Jiyoung Kim, Jessica Curtis, Christopher A Moad, Christina M Wohler, Fred E Indig, Wilson de Paula, Dawood B Dudekula, Supriyo De, Yulan Piao, Xiaoling Yang, Jennifer L Martindale, Rafael de Cabo, Myriam Gorospe
Some mitochondrial long noncoding RNAs (lncRNAs) are encoded by nuclear DNA, but the mechanisms that mediate their transport to mitochondria are poorly characterized. Using affinity RNA pull-down followed by mass spectrometry analysis, we found two RNA-binding proteins (RBPs), HuR (human antigen R) and GRSF1 (G-rich RNA sequence-binding factor 1), that associated with the nuclear DNA-encoded lncRNA RMRP and mobilized it to mitochondria. In cultured human cells, HuR bound RMRP in the nucleus and mediated its CRM1 (chromosome region maintenance 1)-dependent export to the cytosol...
May 15, 2016: Genes & Development
Irene Alfaras, Clara Di Germanio, Michel Bernier, Anna Csiszar, Zoltan Ungvari, Edward G Lakatta, Rafael de Cabo
Aging is the major risk factor for cardiovascular diseases, which are the leading cause of death in the United States. Traditionally, the effort to prevent cardiovascular disease has been focused on addressing the conventional risk factors, including hypertension, hyperglycemia, hypercholesterolemia, and high circulating levels of triglycerides. However, recent preclinical studies have identified new approaches to combat cardiovascular disease. Calorie restriction has been reproducibly shown to prolong lifespan in various experimental model animals...
May 13, 2016: Circulation Research
Mashani Mohamad, Sarah Jayne Mitchell, Lindsay Edward Wu, Melanie Yvonne White, Stuart James Cordwell, John Mach, Samantha Marie Solon-Biet, Dawn Boyer, Dawn Nines, Abhirup Das, Shi-Yun Catherine Li, Alessandra Warren, Sarah Nicole Hilmer, Robin Fraser, David Andrew Sinclair, Stephen James Simpson, Rafael de Cabo, David George Le Couteur, Victoria Carroll Cogger
While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis...
August 2016: Aging Cell
Michel Bernier, Devin Wahl, Ahmed Ali, Joanne Allard, Shakeela Faulkner, Artur Wnorowski, Mitesh Sanghvi, Ruin Moaddel, Irene Alfaras, Julie A Mattison, Stefano Tarantini, Zsuzsanna Tucsek, Zoltan Ungvari, Anna Csiszar, Kevin J Pearson, Rafael de Cabo
Previous studies have shown positive effects of long-term resveratrol (RSV) supplementation in preventing pancreatic beta cell dysfunction, arterial stiffening and metabolic decline induced by high-fat/high-sugar (HFS) diet in nonhuman primates. Here, the analysis was extended to examine whether RSV may reduce dietary stress toxicity in the cerebral cortex of the same cohort of treated animals. Middle-aged male rhesus monkeys were fed for 2 years with HFS alone or combined with RSV, after which whole-genome microarray analysis of cerebral cortex tissue was carried out along with ELISA, immunofluorescence, and biochemical analyses to examine markers of vascular health and inflammation in the cerebral cortices...
May 2016: Aging
Marta Gonzalez-Freire, Alberto Diaz-Ruiz, Rafael de Cabo
No abstract text is available yet for this article.
March 31, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Julia Ariza, José A González-Reyes, Laura Jódar, Alberto Díaz-Ruiz, Rafael de Cabo, José Manuel Villalba
Nuclear factor E2-related factor-2 (Nrf2) is a cap'n'collar/basic leucine zipper (b-ZIP) transcription factor which acts as sensor of oxidative and electrophilic stress. Low levels of Nrf2 predispose cells to chemical carcinogenesis but a dark side of Nrf2 function also exists because its unrestrained activation may allow the survival of potentially dangerous damaged cells. Since Nrf2 inhibition may be of therapeutic interest in cancer, and a decrease of Nrf2 activity may be related with degenerative changes associated with aging, it is important to investigate how the lack of Nrf2 function activates molecular mechanisms mediating cell death...
June 2016: Free Radical Biology & Medicine
Nicole Noren Hooten, Alejandro Martin-Montalvo, Douglas F Dluzen, Yongqing Zhang, Michel Bernier, Alan B Zonderman, Kevin G Becker, Myriam Gorospe, Rafael de Cabo, Michele K Evans
Metformin, an oral hypoglycemic agent, has been used for decades to treat type 2 diabetes mellitus. Recent studies indicate that mice treated with metformin live longer and have fewer manifestations of age-related chronic disease. However, the molecular mechanisms underlying this phenotype are unknown. Here, we show that metformin treatment increases the levels of the microRNA-processing protein DICER1 in mice and in humans with diabetes mellitus. Our results indicate that metformin upregulates DICER1 through a post-transcriptional mechanism involving the RNA-binding protein AUF1...
June 2016: Aging Cell
Jon-Philippe K Hyatt, Lisa Nguyen, Allison E Hall, Ashley M Huber, Jessica C Kocan, Julie A Mattison, Rafael de Cabo, Jeannine R LaRocque, Robert J Talmadge
Shifts in myosin heavy chain (MHC) expression within skeletal muscle can be induced by a host of stimuli including, but not limited to, physical activity, alterations in neural activity, aging, and diet or obesity. Here, we hypothesized that both age and a long-term (2 year) high fat/high sugar diet (HFS) would induce a slow to fast MHC shift within the plantaris, soleus, and extensor digitorum longus (EDL) muscles from rhesus monkeys. Furthermore, we tested whether supplementation with resveratrol, a naturally occurring compound that has been attributed with augmenting aerobic potential through mitochondrial proliferation, would counteract any diet-induced MHC changes by promoting a fast to slow isoform switch...
2016: Frontiers in Physiology
Marta G Novelle, Ahmed Ali, Carlos Diéguez, Michel Bernier, Rafael de Cabo
Even though the inevitable process of aging by itself cannot be considered a disease, it is directly linked to life span and is the driving force behind all age-related diseases. It is an undisputable fact that age-associated diseases are among the leading causes of death in the world, primarily in industrialized countries. During the last several years, an intensive search of antiaging treatments has led to the discovery of a variety of drugs that promote health span and/or life extension. The biguanide compound metformin is widely used for treating people with type 2 diabetes and appears to show protection against cancer, inflammation, and age-related pathologies...
March 2016: Cold Spring Harbor Perspectives in Medicine
Miguel Calvo-Rubio, M Isabel Burón, Guillermo López-Lluch, Plácido Navas, Rafael de Cabo, Jon J Ramsey, José M Villalba, José A González-Reyes
Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils...
June 2016: Aging Cell
Alice Elizabeth Kane, Aniko Huizer-Pajkos, John Mach, Catriona McKenzie, Sarah Jayne Mitchell, Rafael de Cabo, Brett Jones, Victoria Cogger, David G Le Couteur, Sarah Nicole Hilmer
Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for nonacute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and subacute paracetamol overexposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures...
June 2016: Fundamental & Clinical Pharmacology
Amaresh C Panda, Kotb Abdelmohsen, Jennifer L Martindale, Clara Di Germanio, Xiaoling Yang, Ioannis Grammatikakis, Ji Heon Noh, Yongqing Zhang, Elin Lehrmann, Dawood B Dudekula, Supriyo De, Kevin G Becker, Elizabeth J White, Gerald M Wilson, Rafael de Cabo, Myriam Gorospe
Skeletal muscle contains long multinucleated and contractile structures known as muscle fibers, which arise from the fusion of myoblasts into multinucleated myotubes during myogenesis. The myogenic regulatory factor (MRF) MYF5 is the earliest to be expressed during myogenesis and functions as a transcription factor in muscle progenitor cells (satellite cells) and myocytes. In mouse C2C12 myocytes, MYF5 is implicated in the initial steps of myoblast differentiation into myotubes. Here, using ribonucleoprotein immunoprecipitation (RIP) analysis, we discovered a novel function for MYF5 as an RNA-binding protein which associated with a subset of myoblast mRNAs...
March 18, 2016: Nucleic Acids Research
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