Enfermedades raras por patología mitocondrial debidas al déficit en coenzima Q10

La disfunción en la actividad de la mitocondria está relacionada con múltiples enfermedades crónicas asociadas con la vejez y con muchas patologías metabólicas. Entre ellas algunas enfermedades raras causadas por el déficit en la síntesis de coenzima Q10, el único componente lipídico implicado en la actividad de la cadena de transporte de electrones mitocondrial. El déficit en los niveles de este lípido está asociado con enfermedades muy graves caracterizadas esencialmente por sordera, ataxia, mialgia y disfunción renal entre otros síntomas. Hasta el momento se han identificado 12 proteínas implicadas en la síntesis de coenzima Q10 en humanos de las cuales se han identificado mutaciones que producen letalidad en homocigosis y graves problemas incluso en heterocigosis. Por otro lado, también se han encontrado deficiencias secundarias en los niveles de coenzima Q10 asociadas a mutaciones de otras proteínas mitocondriales o a la disfunción mitocondrial relacionada con el envejecimiento o enfermedades metabólicas. Esta deficiencia secundaria podría entorpecer la actividad mitocondrial no solo por enlentecer la actividad de la cadena de transporte de electrones sino por bloquear la actividad de los supercomplejos mitocondriales, recientemente asociados con ciertas patologías. Como el coenzima Q10 también cumple funciones importantes en otras membranas celulares tales como actuar como antioxidante en éstas y regular la actividad de otros antioxidantes como la vitamina E o C, así como regular procesos de señalización, la deficiencia en este lípido puede causar otras múltiples disfunciones que se agravan con la edad. Si bien el tratamiento con coenzima Q10 puede aliviar de alguna manera algunas patologías debidas a la deficiencia primaria, es muy posible que en el caso de la secundaria pueda ser un buen tratamiento de futuro aunque nunca hemos de perder de vista que se trata de una deficiencia derivada de una disfunción previa de la mitocondria.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. Departamento de Biología Celular, Genética y Fisiología Máster Oficial en Biología Celular y Molecular de la Universidad de Málag

Facing Challenges in an Aging World [9th European Congress of Biogerontology]

116 p.It is clear that the amount of people reaching old age is increasing worldwide. During last decades, the percentage of population aged more than 65 has been increasing. In fact, United Nations Organization reports indicate that the percentage of population aged more than 60 years was around a 10% in 1999 in the world but this increase will reach the 20% in 2050. Part of this effect is due to the increase lifespan of humans during last decades. It has been calculated that between 2045 and 2050 the lifespan of people aged 80 years will be around 10 years. It means that the number of nonagenarians and even centenarians will increase soon (United Nations Department of Economics and Social Affairs, World Population Ageing 2013). Currently Europe has reached a 20% of population aged more than 60 years and in 2050 this proportion will be around 30%. Taken into consi-deration the needs of this population, the sustainability of social and health systems needs to be revised. Several initiatives have been proposed to increase health and independen-cy in elderly people. Increasing healthspan in aged population is one of the most important challenges in the near future. For example, the program EIP-AHA (Europa Innovation Partnership on Active and Healthy Ageing) of the European Union pursues three main objectives involved in the increase in health span in European citizens. It is widely known that life habits deeply affect the capacity of cells, organs and tissues. Sedentary life habits and the increasing consume of saturated fatty acids is severely affecting the risk to suffer cardiovascular diseases, obesity, diabetes and metabolic diseases, all of them associated to chronic treatment during ageing. All sections (8) were also accompanied by different posters that have been associated to the different sections in this book. The reader of this book will then find a picture of the different fields included in the study of the biological ageing in different models from molecular to epidemiological aspects. I hope this information will be useful to, at least, understand how complex in the Biogerontology field and how much effort we have to do to increase longevity and, more importantly, health span during ageing

Facing challenges in an ageing world

Editorial.The sponsorship of the following contributors made possible the meeting: Universidad Pablo de Olavide, Centro Andaluz de Biología del Desarrollo, Springer Publishers, International Coenzyme Q10 Association, Sociedad Española de Biología Celular, Universidad Internacional de Andalucía, Junta de Andalucía, Cien por Cien Natural, Pharma Nord Denmark, C. Viral, ThermoFisher Scientific and Cultek.Peer Reviewe

High-intensity interval training combined with vibration and dietary restriction Improves body composition and blood lipids in obese adults: a randomized trial

This study aimed to compare the effect of high-intensity interval training (HIIT) with additional whole-body vibration (WBV) on body composition and lipid profile in obese/overweight adults on a hypocaloric diet. Forty adults were randomly assigned to (a) HIIT and vibration and hypocaloric diet (HIITWBV, n ¼ 13), (b) HIIT and diet (HIIT, n ¼ 14), and (c) diet only (control [CON], n ¼ 13). High-intensity interval training WBV participants trained 3 times per week for 8 weeks (6 sets 1 minute of HIIT, cycling at 90% heart rate peak followed by 1 minute of interset vibration, at a frequency of 18 Hz increasing until 25 Hz with a peak-to- peak displacement of 4 mm. Training volume increased 1 set every 2 weeks until 10 sets). The HIIT group performed HIIT training followed by 2 minutes of passive recovery, while the CON continued with their daily activities combined with calorie restriction. Body composition (body fat and fat-free mass) and biochemical indices (glucose, total cholesterol, high-density lipoprotein cholesterol, and triglycerides) were determined. Following 8 weeks, body fat was significantly reduced by 7.5% and both tri- glycerides and total cholesterol decreased in the HIITWBV group only ( 16.5% and 11.7% respectively). This study suggests that HIIT in combination with WBV and a hypocaloric diet can improve overall lipid profile in overweight/obese individual

The influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction

PMCID: PMC4138957.-- et al.Calorie restriction (CR) has been shown to decrease reactive oxygen species (ROS) production and retard aging in a variety of species. It has been proposed that alterations in membrane saturation are central to these actions of CR. As a step towards testing this theory, mice were assigned to 4 dietary groups (control and 3 CR groups) and fed AIN-93G diets at 95 % (control) or 60 % (CR) of ad libitum for 8 months. To manipulate membrane composition, the primary dietary fats for the CR groups were soybean oil (also used in the control diet), fish oil or lard. Skeletal muscle mitochondrial lipid composition, proton leak, and H2O2 production were measured. Phospholipid fatty acid composition in CR mice was altered in a manner that reflected the n-3 and n-6 fatty acid profiles of their respective dietary lipid sources. Dietary lipid composition did not alter proton leak kinetics between the CR groups. However, the capacity of mitochondrial complex III to produce ROS was decreased in the CR lard compared to the other CR groups. The results of this study indicate that dietary lipid composition can influence ROS production in muscle mitochondria of CR mice. It remains to be determined if lard or other dietary oils can maximize the CRinduced decreases in ROS production. © 2014 Institute of Physiology v.v.i.This work was supported by the National Institutes of Health grants R01 AG028125 and P01 AG025532.Peer Reviewe

Influence of functional capacity on lipid profile, muscle damage and biochemical profile among community-dwelling elderly-people

Under a Creative Commons license.[ES]: [Objetivo]: Describir la influencia que la capacidad funcional tiene sobre el perfil bioquímico y daño muscular, así como analizar la relación existente entre estas variables en personas mayores no institucionalizadas. [Método]: Se utilizó un diseño de corte transversal-observacional en el que se incluyeron 43 sujetos (19 hombres y 24 mujeres). Se analizó la capacidad funcional (T6MW, TUG, CST y PM) y variables bioquímicas (colesterol total, HDL, LDL, triglicéridos, glucosa, GOT, GPT, creatinina y CK). Se establecieron diferencias en función del nivel de capacidad funcional de cada una de las pruebas, así como las relaciones entre cada una de las variables. [Resultados]: Los sujetos que obtuvieron mayores niveles en los test de capacidad funcional obtuvieron resultados más satisfactorios para las diferentes variables de estudio bioquímico (p < 0,05). Estas diferencias se mantuvieron también cuando los datos fueron analizados atendiendo al género. Además, se observó una correlación entre el daño muscular y las diferentes variables de capacidad funcional testadas. [Conclusión]: Este estudio muestra la influencia que la capacidad funcional en mayores presenta sobre parámetros bioquímicos asociados a enfermedades metabólicas o cardiovasculares, así como sobre el daño muscular y sugiere la necesidad de implementar actividades tanto aeróbicas como de fuerza en población mayor.[EN]: [Objective]: To analyze the influence of functional capacity on the biochemical profile and muscle damage and to test the level of relationship between these variables among community-dwelling elderly people. [Method]: A cross-sectional, observational study with 43 participants (19 males and 24 women) was performed. Functional capacity (including 6MWT, TUG test, CST test and Hand grip strength test), and biochemical profile (including total cholesterol, HDL, LDL, triglycerides, glucose, GOT, GPT, creatine and CK) were assessed. Differences on biochemical profile-related variables regarding the functional capacity level were analyzed. The level of relationship between the variables comprising these two domains was also assessed. [Results]: Those participants with a better results in functional capacity variables also achieved the better results in regard of the biochemical parameters measured (p < 0,05). These differences were also maintained after a gender-based analysis. Moreover, relationships between muscle damage and functional capacity variables were also achieved. [Conclusion]: This study shows the influence of the functional capacity on the biochemical parameters (mostly associated to cardiovascular and metabolic diseases) along with the influence that such variables have on the muscle damage and suggest the needed on the implementation of both aerobic and strength training for elderly.El presente trabajo ha sido financiado por la Junta de Andalucía. Jesús del Pozo-Cruz fue galardonado con una beca predoctoral financiada por el proyecto IMD2010-SC002 del Centro Andaluz de Medicina del Deporte, en nombre de la Junta de Andalucía. pen Access funded by Consejería de Educación, Cultura y Deporte de la Junta de Andalucía.Peer Reviewe

Efecto agudo hipotensivo de la combinación de ejercicios basados en caminar y de resistencia en mujeres mayores de 65 años no institucionalizadas

Under a Creative Commons license.[EN]: [Objective]: The aim of this study was to test the effects on blood pressure of a single bout of low-intensity resistance exercise combined with moderate aerobic walk-based exercise performed by active, controlled hypertensive elderly women. [Method]: Forty-two participants were randomized in two types of sessions: exercise session (n = 21), that performed a single bout of combined exercise and control session (n = 21) that keep in rest during the bout. Pre-session, post-session and post-24-hour systolic, diastolic and mean pressure values were evaluated and compared between groups. [Results]: Statistical significant reductions were achieved just after the performed bout (7% of reduction) and 24 hours after the bout (9% of reduction) on the diastolic blood pressure values in the exercise session group. [Conclusions]: In this population, a single bout of combined session is feasible and safe and has a hypotensive effect on diastolic blood pressure in both immediately and after 24 hours post exercise.[ES]: [Objetivo]: Comprobar el efecto hipotensivo que una sola sesión de ejercicio combinado puede tener sobre la presión arterial de mujeres hipertensas controladas y mayores de 65 años. [Método]: Cuarenta y dos participantes fueron asignadas aleatoriamente a dos grupos de sesiones: sesión de entrenamiento (n = 21) que realizó una sola sesión de ejercicios combinados y sesión control (n = 21) que mantuvo reposo durante la misma. Antes, después y tras 24 horas desde la sesión, los valores de presión sistólica, diastólica y medios fueron evaluados y comparados entre grupos. [Resultados]: Se encontraron diferencias estadísticamente significativas entre los grupos tras la realización de la sesión (7% de reducción) y tras 24 horas (9% de reducción) en los valores de presión arterial diastólica media del grupo experimental. [Conclusiones]: En esta población una sola sesión de ejercicio combinado se propone como aplicable y segura y tiene un efecto hipotensivo en la presión diastólica tanto inmediatamente después como pasadas 24 horas de la intervención.The present study was supported by grants from the Government of Andalusia. Andalusia Center for Development Biology provided human and infrastructure resources. Jesús del Pozo-Cruz was awarded a predoctoral fellowship funded by the proyect IMD2010-SC002 from the Andalusia Center of Sport Medicine on behalf of the Government of Andalusia.Open Access funded by Consejería de Educación, Cultura y Deporte de la Junta de Andalucía.Peer Reviewe

Cardiac fibroblasts display endurance to ischemia, high ROS control and elevated respiration regulated by the JAK2/STAT pathway

Cardiac fibroblast; Cellular respiration; SurvivalFibroblast cardíac; Respiració cel·lular; SupervivènciaFibroblasto cardiaco; Respiración celular; SupervivenciaCardiovascular diseases are the leading cause of death globally and more than four out of five cases are due to ischemic events. Cardiac fibroblasts (CF) contribute to normal heart development and function, and produce the post-ischemic scar. Here, we characterize the biochemical and functional aspects related to CF endurance to ischemia-like conditions. Expression data mining showed that cultured human CF (HCF) express more BCL2 than pulmonary and dermal fibroblasts. In addition, gene set enrichment analysis showed overrepresentation of genes involved in the response to hypoxia and oxidative stress, respiration and Janus kinase (JAK)/Signal transducer and Activator of Transcription (STAT) signaling pathways in HCF. BCL2 sustained survival and proliferation of cultured rat CF, which also had higher respiration capacity and reactive oxygen species (ROS) production than pulmonary and dermal fibroblasts. This was associated with higher expression of the electron transport chain (ETC) and antioxidant enzymes. CF had high phosphorylation of JAK2 and its effectors STAT3 and STAT5, and their inhibition reduced viability and respiration, impaired ROS control and reduced the expression of BCL2, ETC complexes and antioxidant enzymes. Together, our results identify molecular and biochemical mechanisms conferring survival advantage to experimental ischemia in CF and show their control by the JAK2/STAT signaling pathway. The presented data point to potential targets for the regulation of cardiac fibrosis and also open the possibility of a general mechanism by which somatic cells required to acutely respond to ischemia are constitutively adapted to survive it.This research was funded by Ministerio de Ciencia e Innovación (MICINN), Gobierno de España, grant numbers SAF2013-44942-R and PID2019-104509RB-I00 to DS; Fundació La Marató TV3, grant number 20153810 to D.S; A.B. holds a contract from Fundació La Marató TV3 and IRBLleida/Diputació de Lleida; Generalitat de Catalunya, (AGAUR) grant number 2017SGR996 to DS; PP-G Laboratory support was obtained through research grants from MICINN (SAF2017/88275R) and CIBERONC (CB16/12/00334); JI and MR-M Laboratory support was obtained from Instituto de Salud Carlos III (ISCIII-FIS) grant PI19-01196; AZ Laboratory support was obtained through research grants from MICINN (PID2019-106209RB-I00), and the Generalitat de Catalunya, (AGAUR) grant number 2017SGR1015. AZ is a recipient of an ICREA ‘Academia’ Award (Generalitat de Catalunya). We gratefully acknowledge institutional funding from the MINECO through the Centres of Excellence Severo Ochoa Award, and from the CERCA Programme of the Generalitat de Catalunya

Mitochondrial ultrastructure and markers of dynamics in hepatocytes from aged, calorie restricted mice fed with different dietary fats

PMCID: PMC4104696In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructure as well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18. months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fats: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CR was studied as well. Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supporting the idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.Supported by NIH grant 1R01AG028125-01A1 (to JJR, PN and JMV), Ministerio de Economía y Competitividad and European FEDERBFU2011-23578 (to JMV), Junta de Andalucía Proyectos de Excelencia grant P09-CVI-4887 (to JMV), Junta de Andalucía Proyectos Internacionales (to JMV), and BIO-276 (Junta de Andalucía and the University of Córdoba, to JMV and EGC). JALD and LFdR were funded by predoctoral fellowships of the Spanish Ministerio de Educación and by BIO-276. HK was funded by a predoctoral fellowship of the Agencia Española de Cooperación Internacional al Desarrollo and by BIO-276.Peer Reviewe

Mitochondrial dynamics in hepatocytes from mice fed caloric restriction diets with different fat sources

Resumen del trabajo presentado al XIV Congresos de la Sociedad Española de Biología Celular, celebrado en Málaga del 12 al 15 de diciembre de 2011.Peer reviewe