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Rafael de Cabo

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https://www.readbyqxmd.com/read/29240911/caloric-restriction-research-new-perspectives-on-the-biology-of-aging
#1
Rozalyn M Anderson, David G Le Couteur, Rafael de Cabo
No abstract text is available yet for this article.
December 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29167747/health-benefits-of-late-onset-metformin-treatment-every-other-week-in-mice
#2
Irene Alfaras, Sarah J Mitchell, Hector Mora, Darisbeth Rosario Lugo, Alessandra Warren, Ignacio Navas-Enamorado, Vickie Hoffmann, Christopher Hine, James R Mitchell, David G Le Couteur, Victoria C Cogger, Michel Bernier, Rafael de Cabo
Chronic 1% metformin treatment is nephrotoxic in mice, but this dose may nonetheless confer health benefits if given intermittently rather than continuously. Here, we examined the effects of 1% metformin given every-other week (EOW) or two consecutive weeks per month (2WM) on survival of 2-year-old male mice fed standard chow. EOW and 2WM mice had comparable life span compared with control mice. A significant reduction in body weight within the first few weeks of metformin treatment was observed without impact on food consumption and energy expenditure...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29158814/dna-methylation-of-mir-7-is-a-mechanism-involved-in-platinum-response-through-mafg-overexpression-in-cancer-cells
#3
Olga Vera, Julia Jimenez, Olga Pernia, Carlos Rodriguez-Antolin, Carmen Rodriguez, Fatima Sanchez Cabo, Javier Soto, Rocio Rosas, Sara Lopez-Magallon, Isabel Esteban Rodriguez, Ana Dopazo, Federico Rojo, Cristobal Belda, Rafael Alvarez, Jaime Valentin, Javier Benitez, Rosario Perona, Javier De Castro, Inmaculada Ibanez de Caceres
One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines...
2017: Theranostics
https://www.readbyqxmd.com/read/29136099/sex-and-aging
#4
David G Le Couteur, Rozalyn M Anderson, Rafael de Cabo
No abstract text is available yet for this article.
November 9, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29126143/understanding-how-dogs-age-longitudinal-analysis-of-markers-of-inflammation-immune-function-and-oxidative-stress
#5
Janet E Alexander, Alison Colyer, Richard M Haydock, Michael G Hayek, JeanSoon Park, Rafael de Cabo
As in human populations, advances in nutrition and veterinary care have led to an increase in the lifespan of companion animals. Detrimental physiological changes occurring later in life must be understood before interventions can be made to slow or reduce them. One important aspect of human aging is upregulation of the inflammatory response and increase in oxidative damage resulting in pathologies linked to chronic inflammation. To determine whether similar processes occur in the aging dog, changes in markers of inflammation and oxidative stress were investigated in 80 Labrador retrievers from adulthood to the end of life...
November 6, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29121176/breaking-the-ceiling-of-human-maximal-lifespan
#6
Moshe Shay Ben-Haim, Yariv Kanfi, Sarah J Mitchel, Noam Maoz, Kelli Vaughan, Ninette Amariglio, Batia Lerrer, Rafael de Cabo, Gideon Rechavi, Haim Y Cohen
While average human life expectancy has increased dramatically in the last century, the maximum lifespan has only modestly increased. These observations prompted the notion that human lifespan might have reached its maximal natural limit of ~115 years. To evaluate this hypothesis, we conducted a systematic analysis of all-cause human mortality throughout the 20 th century. Our analyses revealed that, once cause of death is accounted for, there is a proportional increase in both median age of death and maximum lifespan...
November 7, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29028259/stem-cell-transplantation-for-frailty
#7
David G Le Couteur, Rozalyn M Anderson, Anne B Newman, Rafael de Cabo
No abstract text is available yet for this article.
October 12, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28977341/caloric-restriction-study-design-limitations-in-rodent-and-nonhuman-primate-studies
#8
Kelli L Vaughan, Tamzin Kaiser, Robert Peaden, R Michael Anson, Rafael de Cabo, Julie A Mattison
For a century, we have known that caloric restriction influences aging in many species. However, only recently it was firmly established that the effect is not entirely dependent on the calories provided. Instead, rodent and nonhuman primate models have shown that the rate of aging depends on other variables, including the macronutrient composition of the diet, the amount of time spent in the restricted state, age of onset, the gender and genetic background, and the particular feeding protocol for the control group...
June 13, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28962651/hexokinases-link-dj-1-to-the-pink1-parkin-pathway
#9
David N Hauser, Adamantios Mamais, Melissa M Conti, Christopher T Primiani, Ravindran Kumaran, Allissa A Dillman, Rebekah G Langston, Alexandra Beilina, Joseph H Garcia, Alberto Diaz-Ruiz, Michel Bernier, Fabienne C Fiesel, Xu Hou, Wolfdieter Springer, Yan Li, Rafael de Cabo, Mark R Cookson
BACKGROUND: Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 and parkin operate in pathways that preserve mitochondrial integrity, but the function of DJ-1 and how it relates to PINK1 and parkin is poorly understood. METHODS: A series of unbiased high-content screens were used to analyze changes at the protein, RNA, and metabolite level in rodent brains lacking DJ-1. Results were validated using targeted approaches, and cellular assays were performed to probe the mechanisms involved...
September 29, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28932108/cognitive-and-behavioral-evaluation-of-nutritional-interventions-in-rodent-models-of-brain-aging-and-dementia
#10
REVIEW
Devin Wahl, Sean Cp Coogan, Samantha M Solon-Biet, Rafael de Cabo, James B Haran, David Raubenheimer, Victoria C Cogger, Mark P Mattson, Stephen J Simpson, David G Le Couteur
Evaluation of behavior and cognition in rodent models underpins mechanistic and interventional studies of brain aging and neurodegenerative diseases, especially dementia. Commonly used tests include Morris water maze, Barnes maze, object recognition, fear conditioning, radial arm water maze, and Y maze. Each of these tests reflects some aspects of human memory including episodic memory, recognition memory, semantic memory, spatial memory, and emotional memory. Although most interventional studies in rodent models of dementia have focused on pharmacological agents, there are an increasing number of studies that have evaluated nutritional interventions including caloric restriction, intermittent fasting, and manipulation of macronutrients...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28649426/conserved-and-species-specific-molecular-denominators-in-mammalian-skeletal-muscle-aging
#11
Evi M Mercken, Miriam Capri, Bethany A Carboneau, Maria Conte, Juliana Heidler, Aurelia Santoro, Alejandro Martin-Montalvo, Marta Gonzalez-Freire, Husam Khraiwesh, José A González-Reyes, Ruin Moaddel, Yongqing Zhang, Kevin G Becker, José M Villalba, Julie A Mattison, Ilka Wittig, Claudio Franceschi, Rafael de Cabo
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28610949/calorie-restriction-in-rodents-caveats-to-consider
#12
REVIEW
Donald K Ingram, Rafael de Cabo
The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward...
October 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28603085/kaempferol-increases-levels-of-coenzyme-q-in-kidney-cells-and-serves-as-a-biosynthetic-ring-precursor
#13
Lucía Fernández-Del-Río, Anish Nag, Elena Gutiérrez Casado, Julia Ariza, Agape M Awad, Akil I Joseph, Ohyun Kwon, Eric Verdin, Rafael de Cabo, Claus Schneider, Jorge Z Torres, María I Burón, Catherine F Clarke, José M Villalba
Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q10, but due to its highly lipophilic nature, Q10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q...
September 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28549083/a-comparison-of-two-mouse-frailty-assessment-tools
#14
Alice E Kane, Aniko Huizer-Pajkos, John Mach, Sarah J Mitchell, Rafael de Cabo, David G Le Couteur, Susan E Howlett, Sarah N Hilmer
The mouse clinical frailty index and the mouse frailty phenotype assessment are two recently developed tools used to assess frailty in mice. The objectives of this study were to investigate whether the same mice are identified as frail with both tools and to examine the association of each of the assessment tools with age and frailty-related outcomes. Frailty was measured using both tools in old (~24 months; n = 36) C57BL/6 male mice. After 2 weeks, blood pressure and heart rate were measured and serum samples were collected for analysis of alanine aminotransferase, creatinine, and albumin levels...
July 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28487241/influence-of-anaerobic-and-aerobic-exercise-on-age-related-pathways-in-skeletal-muscle
#15
Ignacio Navas-Enamorado, Michel Bernier, Gloria Brea-Calvo, Rafael de Cabo
No abstract text is available yet for this article.
August 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28403379/effect-of-resveratrol-on-walking-performance-in-older-people-with-peripheral-artery-disease-the-restore-randomized-clinical-trial
#16
Mary M McDermott, Christiaan Leeuwenburgh, Jack M Guralnik, Lu Tian, Robert Sufit, Lihui Zhao, Michael H Criqui, Melina R Kibbe, James H Stein, Donald Lloyd-Jones, Stephen D Anton, Tamar S Polonsky, Ying Gao, Rafael de Cabo, Luigi Ferrucci
Importance: Research shows that resveratrol, a sirtuin activator in red wine, improves exercise endurance and skeletal-muscle oxidative metabolism in animals and may enhance vascular function in humans. Resveratrol supplement sales exceed $30 million annually in the United States, but few data are available regarding its efficacy in humans. Objective: To determine whether resveratrol, 125 mg/d or 500 mg/d, improves the 6-minute walk performance in patients with peripheral artery disease (PAD)...
August 1, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28329314/sirt1-polymorphisms-and-serum-induced-sirt1-protein-expression-in-aging-and-frailty-the-champ-study
#17
Shajjia Razi, Victoria C Cogger, Marina Kennerson, Vicky L Benson, Aisling C McMahon, Fiona M Blyth, David J Handelsman, Markus J Seibel, Vasant Hirani, Vasikaran Naganathan, Louise Waite, Rafael de Cabo, Robert G Cumming, David G Le Couteur
The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older...
July 1, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28133767/the-human-longevity-gene-homolog-indy-and-interleukin-6-interact-in-hepatic-lipid-metabolism
#18
Christian von Loeffelholz, Stefanie Lieske, Frank Neuschäfer-Rube, Diana M Willmes, Nathanael Raschzok, Igor M Sauer, Jörg König, Martin F Fromm, Paul Horn, Antonios 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-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis...
August 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
#19
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
#20
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
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