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Rafael de Cabo

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https://www.readbyqxmd.com/read/28133767/the-human-longevity-gene-homolog-indy-and-interleukin-6-interact-in-hepatic-lipid-metabolism
#1
Christian von Loeffelholz, Stefanie Lieske, Frank Neuschäfer-Rube, Diana M Willmes, Nathanael Raschzok, Igor M Sauer, Jörg König, Martin Fromm, Paul Horn, Antonis Chatzigeorgiou, Andrea Pathe-Neuschäfer-Rube, Jens Jordan, Andreas F H Pfeiffer, Geltrude Mingrone, Stefan R Bornstein, Peter Stroehle, Christoph Harms, F Thomas Wunderlich, Stephen L Helfand, Michel Bernier, Rafael de Cabo, Gerald I Shulman, Triantafyllos Chavakis, Gerhard P Püschel, Andreas L Birkenfeld
Reduced expression of the Indy ('I am Not Dead, Yet') gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane associated citrate transporter expressed highly in the liver, protects mice from high-fat diet and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We aimed to study a possible role of mIndy in human hepatic fat metabolism. In obese, insulin resistant patients with NAFLD, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis...
January 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28094793/caloric-restriction-improves-health-and-survival-of-rhesus-monkeys
#2
Julie A Mattison, Ricki J Colman, T Mark Beasley, David B Allison, Joseph W Kemnitz, George S Roth, Donald K Ingram, Richard Weindruch, Rafael de Cabo, Rozalyn M Anderson
Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity...
January 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28076763/osteocalcin-signaling-in-myofibers-is-necessary-and-sufficient-for-optimum-adaptation-to-exercise
#3
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
No abstract text is available yet for this article.
January 10, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/27923032/spermidine-to-the-rescue-for-an-aging-heart
#4
Rafael de Cabo, Pácido Navas
No abstract text is available yet for this article.
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27921031/amniotic-epithelial-cells-a-new-tool-to-combat-aging-and-age-related-diseases
#5
Clara Di Germanio, Michel Bernier, Rafael de Cabo, Barbara Barboni
The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27875656/involvement-of-jnk-in-tnf%C3%AE-driven-remodelling
#6
Irene Mj Eurlings, Niki L Reynaert, Cheryl van de Wetering, Scott W Aesif, Evi M Mercken, Rafael de Cabo, Jos L van der Velden, Yvonne M Janssen-Heininger, Emiel F M Wouters, Mieke A Dentener
Lung tissue remodeling in chronic obstructive pulmonary disease (COPD) is characterized by airway wall thickening and/or emphysema. Although the bronchial and alveolar compartments are functionally independent entities, we recently showed comparable alterations in matrix composition comprised of decreased elastin content and increased collagen and hyaluronan contents of alveolar and small airway walls. Out of several animal models tested SPC-TNFα mice showed remodelling in alveolar and airway walls similar to what is observed in COPD patients...
November 22, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27822024/animal-models-of-frailty-current-applications-in-clinical-research
#7
REVIEW
Alice E Kane, Sarah N Hilmer, John Mach, Sarah J Mitchell, Rafael de Cabo, Susan E Howlett
The ethical, logistical, and biological complications of working with an older population of people inherently limits clinical studies of frailty. The recent development of animal models of frailty, and tools for assessing frailty in animal models provides an invaluable opportunity for frailty research. This review summarizes currently published animal models of frailty including the interleukin-10 knock-out mouse, the mouse frailty phenotype assessment tool, and the mouse clinical frailty index. It discusses both current and potential roles of these models in research into mechanisms of frailty, interventions to prevent/delay frailty, and the effect of frailty on outcomes...
2016: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/27737375/the-impact-of-the-use-of-different-types-of-gloves-and-bare-hands-for-preparation-of-clean-surgical-instruments
#8
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
https://www.readbyqxmd.com/read/27714847/the-effects-of-aging-and-sex-steroid-deficiency-on-the-murine-skeleton-are-independent-and-mechanistically-distinct
#9
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
https://www.readbyqxmd.com/read/27515817/novel-rna-binding-activity-of-nqo1-promotes-serpina1-mrna-translation
#10
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...
October 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27411588/fasting-mimicking-diet-reduces-ho-1-to-promote-t%C3%A2-cell-mediated-tumor-cytotoxicity
#11
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
https://www.readbyqxmd.com/read/27355990/nutritional-strategies-to-optimise-cognitive-function-in-the-aging-brain
#12
REVIEW
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
https://www.readbyqxmd.com/read/27304509/effects-of-sex-strain-and-energy-intake-on-hallmarks-of-aging-in-mice
#13
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
https://www.readbyqxmd.com/read/27304508/osteocalcin-signaling-in-myofibers-is-necessary-and-sufficient-for-optimum-adaptation-to-exercise
#14
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
https://www.readbyqxmd.com/read/27259996/conditioned-medium-derived-from-rat-amniotic-epithelial-cells-confers-protection-against-inflammation-cancer-and-senescence
#15
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...
June 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27198227/hur-and-grsf1-modulate-the-nuclear-export-and-mitochondrial-localization-of-the-lncrna-rmrp
#16
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...
15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27174954/pharmacological-strategies-to-retard-cardiovascular-aging
#17
REVIEW
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
https://www.readbyqxmd.com/read/27095270/ultrastructure-of-the-liver-microcirculation-influences-hepatic-and-systemic-insulin-activity-and-provides-a-mechanism-for-age-related-insulin-resistance
#18
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
https://www.readbyqxmd.com/read/27070252/resveratrol-supplementation-confers-neuroprotection-in-cortical-brain-tissue-of-nonhuman-primates-fed-a-high-fat-sucrose-diet
#19
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
https://www.readbyqxmd.com/read/27034507/17%C3%AE-estradiol-a-novel-therapeutic-intervention-to-target-age-related-chronic-inflammation
#20
EDITORIAL
Marta Gonzalez-Freire, Alberto Diaz-Ruiz, Rafael de Cabo
No abstract text is available yet for this article.
January 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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