Effect of a caloric restriction based on the Mediterranean diet and intake of traditional Mediterranean foods on the expression of microRNAs regulating molecular processes associated with aging

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología. Fecha de lectura: 10-01-2019The demographic trend in Europe shows a gradual aging of the population. Aging is a process that have been associated with the development of age-related diseases as diabetes, cardiovascular disease or cancer. Immune defeat, cognitive impairment or the loss of proper regulation of sensory pathways of metabolic state such as IGF-1/PI3K/AKT/FOXO and AMPK/SIRT1/mTOR pathways are other hallmarks of aging. Aging is an irreversible process, but it can be modulable, and it is also affected by environmental factors as diet. In this sense, a healthy dietary pattern as Mediterranean Diet or its specific foods and caloric restriction have been postulated as the most important interventions that allow increasing the expectancy and quality of life. MicroRNAs, short non-coding RNA sequences are key epigenetic regulators of these nutrient sensing pathways. This thesis is focused in the nutritional modulation of microRNAs related to cardiovascular disease and aging and regulating nutrient sensing pathways. For this purpose, we carried out different intervention studies with functional extra virgin olive oil enriched with its own polyphenols in healthy patients (VOHF study), beer and non-alcoholic beer in volunteers at high cardiovascular risk (miRoBeer study) and Mediterranean Diet (MD) with/without caloric restriction in late adults with metabolic syndrome (PREDIMED-PLUS study). In addition, it has been tested the presence of exogenous microRNAs in human plasma. The results obtained in this thesis showed first, the non-detection of exogenous microRNAs in human plasma in nor in in olive oil and beer. With the VOHF study, we observed that functional extra virgin olive oil consistently regulated let-7e, microRNA implicated in insulin signaling and inflammation, miR-17-92 cluster, which is a regulator of IGF-1/PI3K/AKT/FOXO and AMPK/SIRT1/mTOR pathways and miR-328, implicated in hypertension and cardiovascular disease. In miRoBeer study we observed a downregulation after non-alcoholic beer intake and an upregulation after beer intake of macrophages miR-17-92 cluster, miR-26b, miR-145, miR-223 and circulating levels of miR-17-92 cluster, miR-155 and a downregulation of miR-320 in both types of beer suggesting an anti-inflammatory microRNA profile but a worse glucose homeostasis. In additions, we observed a correlation between macrophage and circulating levels of miR-328, let-7e, miR-92 and miR-26b suggesting a link between both. Last, we observed a downregulation after 1 year of treatment with a hypocaloric Mediterranean diet with physical activity of macrophage miR-130a and miR-30c in MD in PREDIMED-PLUS study and a lower population of senescent lymphocytes. To conclude, we suggest that one of the mechanisms by MD and their associated foods have beneficial effects on human health could be the modulation of microRNAs and the observed modulation of circulating microRNAs suggest the detection of putative biomarkers of nutritional response, but further studies are necessary to confirm this effect.Europa muestra un envejecimiento gradual de la población que tiene asociado el desarrollo de enfermedades como la diabetes, las enfermedades cardiovasculares o el cáncer además de la disfunción inmune, el deterioro cognitivo o la pérdida de la regulación de vías sensoras del estado metabólico, como la vía de IGF1/PI3K/AKT/FOXO y la vía de AMPK/SIRT1/mTOR. El envejecimiento es un proceso irreversible, pero que a su vez puede ser modulable, y que está afectado por factores ambientales como la dieta. En este sentido, un patrón dietético saludable como la dieta mediterránea o sus alimentos típicos y la restricción calórica se han postulado como algunas de las intervenciones más importantes que permiten aumentar la calidad y esperanza de vida. Los microRNAs, secuencias cortas de ARN no codificantes, son reguladores epigenéticos clave de estas vías sensoras de nutrientes. Esta tesis está centrada en la modulación de microRNAs relacionados con las enfermedades cardiovasculares, envejecimiento y vías sensoras de nutrientes. Para ello, hemos realizado diferentes estudios de intervención con aceite de oliva virgen extra funcional enriquecido en sus propios polifenoles en pacientes sanos (estudio VOHF), un estudio con cerveza y cerveza sin alcohol en voluntarios con alto riesgo cardiovascular (estudio miRoBeer) y un estudio con Dieta Mediterránea (DM) con/sin restricción calórica en adultos de edad avanzada con síndrome metabólico (estudio PREDIMED-PLUS). Además, se ha testado la presencia de microRNAs exógenos en plasma humano. Los resultados obtenidos en esta tesis muestran, en primer lugar, la no detección de microRNAs exógenos en plasma humano así como en aceite de oliva y cerveza. En el estudio VOHF observamos que el aceite de oliva virgen extra funcional regulaba consistentemente let-7e, microRNA implicado en la cascada de señalización de la insulina e inflamación, miR-17-92 cluster, regulador del IGF-1/PI3K/AKT/FOXO y AMPK/SIRT1/mTOR y miR-328, implicado en la hipertensión y las enfermedades cardiovasculares. En el estudio miRoBeer se observó una sobreexpresión en cerveza con alcohol y una represión en cerveza sin alcohol del miR-17-92 cluster, miR-26b, miR-145, miR-223 en macrófagos y en los niveles circulantes de miR-17-92 cluster, miR-155 siendo una represión de miR-320 en ambos tipos de cerveza, sugiriendo un perfil de microRNAs antiinflamatorio pero con una peor homeostasis de la glucosa. Además, observamos correlaciones entre los niveles de macrófagos y circulantes de miR-328, let-7e, miR-92 y miR-26b, sugiriendo un vínculo entre ambos. Por último, observamos una represión de miR-130a y miR-30c después de 1 año de tratamiento con DM con restricción calórica en el estudio PREDIMED-PLUS, además de una menor población de linfocitos senescentes. Por todo ello sugerimos que uno de los mecanismos por los que la DM y sus alimentos asociados tienen efectos beneficiosos en la salud humana podría ser la modulación de los microRNAs además de que la modulación observada de microRNAs circulantes sugiere la detección de biomarcadores de respuesta nutricional, aunque son necesarios más estudios para confirmar este efecto.Esta tesis ha sido realizada gracias a las Ayudas Merck Serono de Investigación otorgadas por la Fundación Salud 2000 además de un contrato en IMDEA Alimentación financiado por fondos FEDER europeos así como fondos de la Comunidad Autónoma de Madri

Evaluación de la competencia transversal “Pensamiento crítico” en el GADE-UPV

[ES] En este artículo se describen las diferentes maneras en que se evalúa la competencia transversal “Pensamiento crítico” en la Facultad de Administración y Dirección de Empresas de la UPV. Existe un proyecto institucional de competencias transversales en la universidad que enmarca este proceso. Mostramos que se dan diferentes formas de evaluación de la competencia transversal, incluso con cambios entre cursos dentro de una misma asignatura. Esta situación se debe a dificultades encontradas en relación al tiempo disponible, a la actitud de los alumnos hacia las competencias transversales y al tamaño de grupo. Además, es difícil evaluar aisladamente la adquisición de esta competencia transversal de otras como por ejemplo resolución de problemas. La diversidad de formas de evalua r esta competencia contribuye a cierta confusión acerca de las consecuencias de la evaluación particular en cada asignatura, y por tanto, se concluye proponiendo una simplificación.[EN] This paper describes how different subjects in the Business Administration Faculty of the UPV assess the soft skill called “critical thought”. This assessment is carried out within the framework of a university program for soft skills, that sets the framework of the process. We show that different assessment procedures are carried out, even with variations over time within a subject. This variability is due to difficulties related to time availability, students attitude and group size. It is also caused by the fact that disentangling this soft skill from otherssuch as problems solving is not always an easy task. Extant multiplicity of assessments of the skill contribute to certain confusion in the final consequence of the assessment in each subject, and hence a simplification is proposed.Martinez Gómez, VD.; Escribá Pérez, C.; Calafat Marzal, MC.; Martínez Gómez, M.; Santamaría Navarro, C.; Villanueva Micó, RJ. (2019). Evaluación de la competencia transversal “Pensamiento crítico” en el GADE-UPV. En JIDDO. I Jornada de innovación en docencia universitaria para la dirección de organizaciones públicas y privadas. Editorial Universitat Politècnica de València. 60-68. https://doi.org/10.4995/JIDDO2019.2019.10171OCS606

Fatty acids homeostasis during fasting predicts protection from chemotherapy toxicity.

Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood from humans and mice before and after 36 or 24 hours of fasting, respectively, and measure lipid composition of erythrocyte membranes, circulating micro RNAs (miRNAs), and RNA expression at peripheral blood mononuclear cells (PBMCs). Fasting coordinately affects the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane; and reduces the expression of insulin signaling-related genes in PBMCs. When fasted for 24 hours before and 24 hours after administration of oxaliplatin or doxorubicin, mice show a strong protection from toxicity in several tissues. Erythrocyte membrane lipids and PBMC gene expression define two separate groups of individuals that accurately predict a differential protection from chemotherapy toxicity, with important clinical implications. Our results reveal a mechanism of fasting associated with lipid homeostasis, and provide biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.General: We thank Prof. Jose Maria. Ordovas for his kind suggestions; nutritionists Helena Marcos-Pasero, Elena Aguilar-Aguilar and Isabel Espinosa-Salinas for their help with volunteers management; Rosa Serrano for her help with animal experiments; Susana Molina for her advice with PBMC isolation; Luisa Mariscal, Domingo Fernandez, Lola Martinez, Diego Megias, Patricia Gonzalez, Fernando Pelaez, Anabel Sanz, Carolina Pola, Celia de la Calle, Ana Ortega, Ana Sagrera, Jose Miguel Frade, Elena Lopez-Guadamillas, Maribel Munoz, Susana Llanos, Andres Fernandez, Aranzazu Sierra, Andres Lopez, Noemi Haro and Ildefonso Rodriguez for their excellent technical and scientific support. Work at the laboratory of P.J.F.M. is funded by the Ramon Areces Foundation, (CIVP18A3891), Asociacion Espanola contra el Cancer-AECC (SIRTBIO-LABAE18008FERN), a Ramon y Cajal Award from the Spanish Ministry of Science, Innovation and Universities (MICINN) (RYC-2017-22335), RETOS projects Program of MICINN (SAF2017-85766-R) and the Portuguese Foundation for Science and Technology (FCT-MCTES, SFRH/BD/124022/2016). Work at the laboratory of ARM was funded by the MICINN (PID2019-110183RB-C21), Regional Government of Community of Madrid (P2018/BAA-4343-ALIBIRD2020-CM) and the Ramon Areces Foundation. Work at the laboratory of A.D.R. Funded by the Comunidad de Madrid-Talento Grant 2018-T1/BMD-11966 and the MICINN PID-2019-106893RA-100. Work at the laboratory of L.D. is funded by projects from the Health Research Fund (ISCIII FIS PI14/01374 and FISPI17/00508) and from a Manuel de Oya research fellowship from the Beer and Health Foundation. Work at the laboratory of A.E. is funded by a Ramon y Cajal Award from MICINN (RYC-2013-13546) and RETOS projects Program of the MICINN, co-funded by the European Regional Development Fund (ERDF) (SAF2015-67538-R). Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Council (ERC-2014-AdG/669622), and the "laCaixa" Foundation.S

Diario de Burgos : de avisos y noticias: Año LXXV Número 23026 - 1965 noviembre 9

Copia digital. España : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201

Lifestyle and Health-Related Quality of Life Relationships Concerning Metabolic Disease Phenotypes on the Nutrimdea Online Cohort

Obesity, diabetes and cardiovascular events are non-communicable diseases (NCDs) directly related to lifestyle and life quality. Rises on NCDs rates are leading to increases in early deaths concerning metabolic morbidities. Health-related quality of life (HRQoL) has been described as a subjective perception about the influence of health and personal features on human well-being. This study aimed to characterize phenotypic and lifestyle roles on the occurrence of metabolic diseases and determine the potential mutual interactions and with HRQoL. Data from an online adult population (NUTRiMDEA study, n = 17,332) were used to estimate an adapted Obesogenic Score (ObS), while logistic regression analyses were fitted in order to examine relevant factors related to the prevalence of different metabolic diseases including HRQoL. Sex and age showed significant differences depending on lifestyle and metabolic health (p < 0.05). Adherence to the Mediterranean diet and physical activity showed a mutual interaction concerning ObS (p < 0.001), as well with metabolic health (p = 0.044). Furthermore, metabolic diseases showed own features related to sociodemographic and lifestyle characteristics in this population. Metabolic syndrome components may be differently influenced by diverse lifestyle or socioeconomic factors which in turn affect the perceived HRQoL. These outcomes should be taken into account individually for a precision medicine and public health purposes

Physical fitness and physical activity association with cognitive function and quality of life: baseline cross-sectional analysis of the PREDIMED-Plus trial

Physical activity (PA) has been hypothesized to be effective to maintaining cognitive function and delay cognitive decline in the elderly, but physical fitness (PF) could be a better predictor of cognitive function. We aimed to study the association between PA and PF with cognitive function and quality of life using cross-sectional data from 6874 participants of the PREDIMED-Plus trial (64.9 ± 4.9 years, 48.5% female). PF and PA were measured with a Chair Stand Test, the REGICOR and Rapid Assessment Physical Activity questionnaires. Cognitive function was measured with Mini-mental State Examination, Control Oral Word Association Test, Trail Making Test and Digit Span tests; whereas health-related quality of life was assessed with the SF36-HRQL test. Cognitive and quality of life scores were compared among PF quartiles and PA levels (low, moderate and high) with ANCOVA and with Chair Stand repetitions and energy expenditure from total PA with multivariable linear regression adjusted for confounding factors. PF associated with higher scores in phonemic and semantic verbal fluency tests and with lower TMT A time. However, PA was not associated with the neurocognitive parameters evaluated. Both PF and PA levels were strongly associated with a better quality of life. We concluded that PF, but not PA, is associated with a better cognitive function. This trial was retrospectively registered at the International Standard Randomized Controlled Trial (ISRCTN89898870, https://www.isrctn.com/ISRCTN89898870?q=ISRCTN89898870&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search) on 07/24/2014.The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/0147, PI14/00636, PI14/00972, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus granted to Jordi Salas-Salvadó, the European Research Council Advanced Research Grant 2013–2018 (340918) granted to Miguel Ángel Martínez-Gonzalez, the Recercaixa grant to Jordi Salas-Salvadó (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016, PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant and FEDER funds (CB06/03). Indira Paz Graniel is granted by the Spanish Ministry of Education, Culture and Sports (FPU 17/01925). None of the funding sources took part in the design, collection, analysis or interpretation of the data, or in the decision to submit the manuscript for publication

The maternal genetic make-up of the Iberian Peninsula between the Neolithic and the Early Bronze Age

Abstract Agriculture first reached the Iberian Peninsula around 5700 BCE. However, little is known about the genetic structure and changes of prehistoric populations in different geographic areas of Iberia. In our study, we focus on the maternal genetic makeup of the Neolithic (~ 5500–3000 BCE), Chalcolithic (~ 3000–2200 BCE) and Early Bronze Age (~ 2200–1500 BCE). We report ancient mitochondrial DNA results of 213 individuals (151 HVS-I sequences) from the northeast, central, southeast and southwest regions and thus on the largest archaeogenetic dataset from the Peninsula to date. Similar to other parts of Europe, we observe a discontinuity between hunter-gatherers and the first farmers of the Neolithic. During the subsequent periods, we detect regional continuity of Early Neolithic lineages across Iberia, however the genetic contribution of hunter-gatherers is generally higher than in other parts of Europe and varies regionally. In contrast to ancient DNA findings from Central Europe, we do not observe a major turnover in the mtDNA record of the Iberian Late Chalcolithic and Early Bronze Age, suggesting that the population history of the Iberian Peninsula is distinct in character