135 results on '"López-Lluch, G."'
Search Results
2. The influence of dietary lipid composition on skeletal muscle mitochondria from mice following eight months of calorie restriction.
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CHEN, Y, HAGOPIAN, K, BIBUS, D, VILLALBA, JM, LÓPEZ-LLUCH, G, NAVAS, P, KIM, K, and RAMSEY, JJ
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Medical Physiology ,Biomedical and Clinical Sciences ,Nutrition ,Aging ,Complementary and Integrative Health ,Prevention ,Animals ,Caloric Restriction ,Dietary Fats ,Fish Oils ,Male ,Mice ,Mice ,Inbred C57BL ,Mitochondria ,Muscle ,Muscle ,Skeletal ,Random Allocation ,Reactive Oxygen Species ,Soybean Oil ,Time Factors ,Dietary lipids ,Energy restriction ,Mitochondria ,Phospholipids ,Reactive oxygen species ,Physiology ,Medical physiology - Abstract
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 H(2)O(2) 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 CR-induced decreases in ROS production.
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- 2014
3. Influence of the level of physical activity on physical fitness, lipid profile and health outcomes in overweight/obese adults with similar nutritional status
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Muñoz-Vera, T., Sañudo, B., del Pozo-Cruz, B., del Pozo-Cruz, J., Lopez-Lluch, G., and Sánchez-Oliver, A.J.
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- 2017
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4. Influencia de la capacidad funcional sobre el perfil lipídico, daño muscular y perfil bioquímico en personas mayores no institucionalizadas
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Del Pozo-Cruz, J., Magaña, M., Ballesteros, M., Porras, M., Rodríguez Bíes, E., Navas, P., and López-Lluch, G.
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- 2013
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5. MITOCHONDRIAL DEFECTS IN THE PARL-DEFICIENT MOUSE MODEL LEAD TO ARRESTED SPERMATOGENESIS AND FERROPTOSIS
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Radaelli, E., Assenmacher, C.A., Verrelle, J., Banerjee, E., Manero, F., Khiati, S., Girona, A., Lopez-Lluch, G., Navas, P., and Spinazzi, M.
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- 2024
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6. Essential role of mitochondrial dynamics in muscle physiology
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López-Lluch, G.
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- 2017
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7. Hypotensive acute effect of a combined resistance and walk-based exercise among over 65-year old community-dwelling women
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del Pozo-Cruz, J., del Pozo-Cruz, B., Rodríguez Bies, E.C., Alfonso-Rosa, R.M., Navas, P., and López-Lluch, G.
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- 2012
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8. Calorie Restriction Induces Mitochondrial Biogenesis and Bioenergetic Efficiency
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López-Lluch, G., Hunt, N., Jones, B., Zhu, M., Jamieson, H., Hilmer, S., Cascajo, M. V., Allard, J., Ingram, D. K., Navas, P., and de Cabo, R.
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- 2006
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9. Mouse liver plasma membrane redox system activity is altered by aging and modulated by calorie restriction
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López-Lluch, G., Rios, M., Lane, M. A., Navas, P., and de Cabo, R.
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- 2005
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10. Induction of endogenous antioxidant enzymes by endurance exercise and resveratrol treatment in the gastrocnemius muscle of old mice: P08r-72
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Bies, Rodríguez E., Velazquez-Dorado, A., Del Pozo-Cruz, J., Arroyo-Hornero, R., Navas, P., and López-Lluch, G.
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- 2012
11. Metabolic changes induced by resveratrol in tumoral cells: P08-61
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Calvo, S. S. C., Rebollo, V. P., Navas, P., and López-Lluch, G.
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- 2012
12. Plasma membrane redox system during HL-60 induced differentiation
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López-Lluch, G., Burón, M. I., Alcaín, F. J., Rodríguez-Aguilera, J. C., and Navas, P.
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- 1995
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13. Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver
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De Cabo, R, Cabello, R, Rios, M, López-Lluch, G, Ingram, D.K, Lane, M.A, and Navas, P
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- 2004
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14. Age-related decrements in dual-task performance: Comparison of different mobility and cognitive tasks. A cross sectional study
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López Lluch, G, Brustio, PR, Magistro, D, Zecca, M, Rabaglietti, E, and Liubicich, ME
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cognition ,Cross-sectional study ,lcsh:Medicine ,Social Sciences ,Audiology ,0302 clinical medicine ,Elderly ,Task Performance and Analysis ,middle aged ,Medicine and Health Sciences ,Attention ,030212 general & internal medicine ,Young adult ,lcsh:Science ,Musculoskeletal System ,comparative study ,Analysis of covariance ,Multidisciplinary ,adult ,Age Factors ,Cognition ,task performance ,aged ,female ,Performance comparison ,Physical Sciences ,Subtraction ,adult, analysis of covariance, cognition, cross-sectional study, dual-task performance (test), female, human, linear regression analysis, major clinical study, male, middle aged, young adult, age, aged, aging, cognition, comparative study, cross-sectional study, physiology, psychology, psychomotor performance, task performance ,young adult ,Anatomy ,Psychology ,psychological phenomena and processes ,dual-task performance (test) ,Research Article ,Elementary cognitive task ,medicine.medical_specialty ,psychology ,behavioral disciplines and activities ,03 medical and health sciences ,male ,medicine ,Humans ,cross-sectional study ,Effects of sleep deprivation on cognitive performance ,human ,analysis of covariance ,Arithmetic ,lcsh:R ,aging ,Cognitive Psychology ,Biology and Life Sciences ,major clinical study ,Young Adults ,Task (computing) ,Cross-Sectional Studies ,age ,Age Groups ,People and Places ,physiology ,linear regression analysis ,psychomotor performance ,Cognitive Science ,lcsh:Q ,Population Groupings ,Physiological Processes ,Organism Development ,030217 neurology & neurosurgery ,Mathematics ,Neuroscience ,Developmental Biology - Abstract
This cross-sectional study investigated the age-related differences in dual-task performance both in mobility and cognitive tasks and the additive dual-task costs in a sample of older, middle-aged and young adults. 74 older adults (M = 72.63±5.57 years), 58 middle-aged adults (M = 46.69±4.68 years) and 63 young adults (M = 25.34±3.00 years) participated in the study. Participants performed different mobility and subtraction tasks under both single- and dual-task conditions. Linear regressions, repeated-measures and one-way analyses of covariance were used, The results showed: significant effects of the age on the dual and mobility tasks (p
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- 2017
15. Essential role of mitochondrial dynamics in muscle physiology
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López-Lluch, G., primary
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- 2016
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16. Relationship between functional capacity and psychosocial profile among community-dwelling elderly-people. A gender based study
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Pozo-Cruz, J. del, Rodriguez Bies, E., Alfonso Rosa, R. M., Pozo-Cruz, B. del, Grimaldi Puyana, Moisés, Navas Lloret, Plácido, and López-Lluch, G.
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Anciano ,Ancianos - Condición física ,Educación física - Abstract
Objetivos: Describir la relación que la capacidad funcional tiene sobre la calidad de vida relacionada con la salud en personas mayores no institucionalizadas. Métodos: 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 psicosociales de calidad de vida (SF-36). 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. Se observó que aquellos sujetos que alcanzaban mayores niveles en las pruebas de capacidad funcional, reportaban mayores puntuaciones en las diferentes dimensiones del SF36. Conclusión y Discusión. Los resultados que presentamos en nuestro estudio sugieren que mayores niveles en la capacidad funcional pueden mejorar la CVRS de personas mayores no institucionalizadas. Objective: to elucidate the relationship between functional capacity and Health-related quality of life among community-dwelling elderly people. Methods: A cross-sectional design was used with 43 subjects (19 males and 24 females). Functional capacity (T6MW, TUG, CST y PM) and Health-related Quality of Life (SF-36) were assessed. Differences based on functional capacity were analyzed. The relationships between the variables of the study were also tested. Results: Those participants reporting better functional capacity values also depicted better scores on SF-36 (p
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- 2013
17. SUN-P142: Bixin Inhibit the Expression of Th2 Cytokines Repressing NF-KB Transcription Factor
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Marrugo, J., Zarate, E., Meza, C., Ocampo, Y., Franco, L., Martinez, B., Hernandez’, L., Lopez-Lluch, G., and Rodriguez-Aguilera, J.C.
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- 2017
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18. Inhibition of COX activity by NSAIDs or ascorbate increases cAMP levels and enhances differentiation in 1α,25-dihydroxyvitamin D3-induced HL-60 cells
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López-Lluch, G., primary, Fernández-Ayala, D.J.M., additional, Alcaín, F.J., additional, Burón, M.I., additional, Quesada, J.M., additional, and Navas, P., additional
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- 2005
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19. Plasma membrane redox system protects cells against oxidative stress
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Rodríguez-Aguilera, J.C., primary, López-Lluch, G., additional, Santos-Ocaña, C., additional, Villalba, J.M., additional, Gómez-Díaz, C., additional, and Navas, P., additional
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- 2000
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20. Role of plasma membrane coenzyme Q on the regulation of apoptosis
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López-Lluch, G., primary, Barroso, M. P., additional, Martín, S. F., additional, Fernández-Ayala, D. J. M., additional, Gómez-Díaz, C., additional, Villalba, J. M., additional, and Navas, P., additional
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- 1999
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21. Ascorbate and α-Tocopherol Prevent Apoptosis Induced by Serum Removal Independent of Bcl-2
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Barroso, M.P., primary, Gómez-Dı́az, C., additional, López-Lluch, G., additional, Malagón, M.M., additional, Crane, F.L., additional, and Navas, P., additional
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- 1997
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22. Relación entre la capacidad funcional y el perfil psicosocial en personas mayores no institucionalizadas. Diferencias basadas en género.
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Del Pozo-Cruz, J., Rodríguez Bies, E., Alfonso-Rosa, R. M ª., Del Pozo-Cruz, B., Grimaldi Puyana, M., Navas, P., and López-Lluch, G.
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PSYCHOSOCIAL factors ,GERIATRIC psychology ,SOCIAL conditions of older people ,HEALTH of older people ,QUALITY of life - Abstract
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- 2013
23. Inhibition of COX activity by NSAIDs or ascorbate increases cAMP levels and enhances differentiation in 1α,25-dihydroxyvitamin D3-induced HL-60 cells
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López-Lluch, G., Fernández-Ayala, D.J.M., Alcaín, F.J., Burón, M.I., Quesada, J.M., and Navas, P.
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ARACHIDONIC acid , *CELLS , *BIOCHEMISTRY , *VITAMIN D , *METABOLITES - Abstract
Abstract: Arachidonic acid metabolism is modulated during differentiation induced by 1α,25(OH)2D3 in HL-60 cells. Antioxidants that affect arachidonic acid metabolism enhance this differentiation program. Ascorbate also enhances differentiation in 1α,25(OH)2D3-induced cells depending on the induction of cAMP. The aim of this work was to study if this cAMP rise depends on modulation of arachidonic acid metabolism by ascorbate. Cyclooxygenase inhibitors, indomethacin and aspirin, increased cAMP levels and also enhanced 1α,25(OH)2D3-induced differentiation in HL-60 cells. Ascorbate did not affect the release of arachidonic acid-derived metabolites but decreased the levels of TXB2 and PGE2, suggesting the inhibition of cyclooxygenase. On the other hand, free arachidonic acid increased both cAMP levels and differentiation in the absence or presence of 1α,25(OH)2D3. Neither cyclooxygenase inhibitors nor ascorbate modified AA effect. Then, inhibition of cyclooxygenase activity by ascorbate could accumulate free arachidonic acid or other metabolites that increase cAMP levels and enhance differentiation in 1α,25(OH)2D3-induced HL-60 cells. [Copyright &y& Elsevier]
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- 2005
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24. Role of plasma membrane coenzyme Q on the regulation of apoptosis
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López-Lluch, G., Barroso, M. P., Martín, S. F., Daniel José Moreno Fernández-Ayala, Gómez-Díaz, C., Villalba, J. M., and Navas, P.
25. Cardiac fibroblasts display endurance to ischemia, high ROS control and elevated respiration regulated by the JAK2/STAT pathway
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Marta Llovera, Marisol Ruiz-Meana, Andrea Irazoki, Carlos Lana, Javier Inserte, Manuel Portero-Otin, Juan G. Valero, Aida Beà, Guillermo López-Lluch, Antonio Zorzano, Daniel Sanchis, Patricia Pérez-Galán, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Fundació La Marató de TV3, Diputació de Lleida, Generalitat de Catalunya, Instituto de Salud Carlos III, Centres de Recerca de Catalunya, Institut Català de la Salut, [Beà A, Lana C] Cell Signaling & Apoptosis Group, Institut de Recerca Biomedica de Lleida (IRBLleida), Universitat de Lleida, Spain. [Valero JG] Department of Hematology-Oncology, Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Centro de Investigacion Biomédica en Red-Oncología (CIBERONC), Barcelona, Spain. [Irazoki A] Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Universitat de Barcelona, Spain. [López-Lluch G] Andalusian Center of Developmental Biology, Pablo de Olavide University, Sevilla, Spain. Centro de Investigación Biomédica en Red Enfermedades Raras (CIBERER), Sevilla, Spain. [Portero-Otín M] Department of Experimental Medicine, IRBLleida, University of Lleida, Lleida, Spain. [Inserte J, Ruiz-Meana M] Laboratori de Cardiologia Experimental, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Spain. Centro de Investigación Biomédica en Red-CV (CIBER-CV), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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STAT3 Transcription Factor ,Cellular respiration ,Survival ,Cardiac fibrosis ,Sistema cardiovascular - Malalties ,Cardiac fibroblast ,Biochemistry ,Antioxidants ,Ischemia ,medicine ,Animals ,STAT3 ,Molecular Biology ,STAT5 ,enfermedades cardiovasculares [ENFERMEDADES] ,biology ,Cardiovascular Diseases [DISEASES] ,Chemistry ,Respiration ,JAK-STAT signaling pathway ,ROS ,Cell Biology ,Fibroblasts ,Janus Kinase 2 ,medicine.disease ,JAK/STAT ,Cell biology ,Rats ,Proto-Oncogene Proteins c-bcl-2 ,biology.protein ,STAT protein ,Signal transduction ,Janus kinase ,Reactive Oxygen Species ,Signal Transduction - Abstract
Cardiovascular 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.
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- 2021
26. Feasibility, Safety, and Effects of an Aerobic Training Program with Blood Flow Restriction on Functional Capacity, and Symptomatology in Women with Fibromyalgia: A Pilot Study.
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Rodríguez-Bautista JC, López-Lluch G, Rodríguez-Torres P, López-Moral Á, Quijada-Carrera J, Bueno-Antequera J, Blanco-Suárez M, Cáceres-Calle Ó, and Munguia-Izquierdo D
- Abstract
Background: Evidence suggests that aerobic training with blood flow restriction is beneficial for treating fibromyalgia. This study evaluated the feasibility, safety, and effects of an aerobic training program with blood flow restriction for women with fibromyalgia., Methods: Thirty-seven women with fibromyalgia were included, and thirteen with an average age of 59 ± 3, a BMI of 26 ± 3, and who were polymedicated started the intervention period. The intervention group performed aerobic exercise with blood flow restriction using occlusive bands placed in the upper part of the rectus femoris, with a total duration of 14 min of restriction divided into two periods of 7 min with a rest period of 3 min and a total session duration of 17 min. Pressure intensity was measured using the visual pain scale (VAS), scoring 7 out of 10 (n = 7). The non-intervention group performed aerobic exercise without restriction of blood flow for the same periods, rest periods, and total duration of the session (n = 6). The intervention included 2 weekly sessions with 72 h between aerobic walking for 9 weeks. Walking was measured individually using the rating of perceived exertion scale (RPE) with an intensity between 6 and 7 out of 10. Visual and verbal support for the VAS and RPE scale was always provided throughout the sessions supervised by the investigator. Functional capacity was assessed using tests (six-minute walk test, incremental shuttle walk test, knee extension and handgrip test by dynamometer, 30 s chair stand test, and timed up-and-go test). Symptomatology was assessed using questionnaires (Widespread Pain Index, Symptom Severity Score, Fibromyalgia Impact Questionnaire, and Multidimensional Fatigue Inventory), and blood samples were collected., Results: There were no adverse effects, and only one participant in the intervention group withdrew. Between-group and intragroup differences showed that the intervention group obtained improvements in the functional tests; CST p = 0.005; 6MWT p = 0.011; Handgrip p = 0.002; TUGT p = 0.002 with reduced impact of the disease according to the questionnaires; FIQ Stiffness p = 0.027 compared with the nonintervention group. Biochemical results remained within normal ranges in both groups., Conclusions: Blood flow-restricted aerobic training may be feasible, safe, and more effective than unrestricted aerobic training as a physical exercise prescription tool to improve cardiorespiratory fitness, strength, balance, and stiffness in women with fibromyalgia.
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- 2024
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27. New variants expand the neurological phenotype of COQ7 deficiency.
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Fabra MA, Paredes-Fuentes AJ, Torralba Carnerero M, Moreno Férnandez de Ayala DJ, Arroyo Luque A, Sánchez Cuesta A, Staiano C, Sanchez-Pintos P, Luz Couce M, Tomás M, Marco-Hernández AV, Orellana C, Martínez F, Roselló M, Caro A, Oltra Soler JS, Monfort S, Sánchez A, Rausell D, Vitoria I, Del Toro M, Garcia-Cazorla A, Julia-Palacios NA, Jou C, Yubero D, López LC, Hernández Camacho JD, López Lluch G, Ballesteros Simarro M, Rodríguez Aguilera JC, Calvo GB, Cascajo Almenara MV, Artuch R, and Santos-Ocaña C
- Abstract
The protein encoded by COQ7 is required for CoQ
10 synthesis in humans, hydroxylating 3-demethoxyubiquinol (DMQ10 ) in the second to last steps of the pathway. COQ7 mutations lead to a primary CoQ10 deficiency syndrome associated with a pleiotropic neurological disorder. This study shows the clinical, physiological, and molecular characterization of four new cases of CoQ10 primary deficiency caused by five mutations in COQ7, three of which have not yet been described, inducing mitochondrial dysfunction in all patients. However, the specific combination of the identified variants in each patient generated precise pathophysiological and molecular alterations in fibroblasts, which would explain the differential in vitro response to supplementation therapy. Our results suggest that COQ7 dysfunction could be caused by specific structural changes that affect the interaction with COQ9 required for the DMQ10 presentation to COQ7, the substrate access to the active site, and the maintenance of the active site structure. Remarkably, patients' fibroblasts share transcriptional remodeling, supporting a modification of energy metabolism towards glycolysis, which could be an adaptive mechanism against CoQ10 deficiency. However, transcriptional analysis of mitochondria-associated pathways showed distinct and dramatic differences between patient fibroblasts, which correlated with the extent of pathophysiological and neurological alterations observed in the probands. Overall, this study suggests that the combination of precise genetic diagnostics and the availability of new structural models of human proteins could help explain the origin of phenotypic pleiotropy observed in some genetic diseases and the different responses to available therapies., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)- Published
- 2024
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28. Cognitive Reserve and Frontotemporal Disorders: Exploring the Relationship Between Education, Physical Activity, and Cognitive Dysfunction in Older Adults.
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Amian JG, Fernandez-Portero C, de la Bella R, Arenilla-Villalba MJ, López-Lluch G, and Alarcon D
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- Humans, Aged, Male, Female, Aged, 80 and over, Cognitive Reserve physiology, Cognitive Dysfunction, Exercise physiology, Exercise psychology, Frontotemporal Dementia psychology, Educational Status
- Abstract
In this study we investigated the relationship between cognitive reserve (CR) proxies, such as education, physical activity (PA), and cognitive dysfunction (CD) in the presence or absence of frontotemporal disorders (FTD). Previous research has suggested that education and PA may delay the onset of CD and reduce the risk of developing dementia. However, it remains unclear whether these CR proxies can protect against CD when FTD is present. We aimed to explore this relationship and determine whether sustained CR may be evident regardless of FTD. We recruited 149 older adults (aged 65-99 years) from community centers where they were voluntarily participating in leisure activities. We used bioelectrical impedance to measure their body composition, and we administered the International PA Questionnaire and the Mini-Mental State Examination to measure their PA and cognitive function, respectively. We used the Frontal Assessment Battery to screen for frontotemporal dementia. Our results showed that people with FTD were older, had lower education, and engaged in less PA, relative to other participants. Regression models revealed that age, education, and PA were significant predictors of FTD. More specifically, FTD was negatively associated with cognitive functioning, and there were significant interaction effects between FTD and education and PA. PA and education were significant predictors of cognitive functioning, and, when values for PA and education were high, they offset the effects of FTD on cognitive function. These findings support impressions that PA and years of education provide an insulating or compensatory effect on cognitive functioning in older adults with executive dysfunction or frontotemporal dementia, highlighting the importance of encouraging both pursuits., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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29. An AlphaFold Structure Analysis of COQ2 as Key a Component of the Coenzyme Q Synthesis Complex.
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Vargas-Pérez MLÁ, Devos DP, and López-Lluch G
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Coenzyme Q (CoQ) is a lipidic compound that is widely distributed in nature, with crucial functions in metabolism, protection against oxidative damage and ferroptosis and other processes. CoQ biosynthesis is a conserved and complex pathway involving several proteins. COQ2 is a member of the UbiA family of transmembrane prenyltransferases that catalyzes the condensation of the head and tail precursors of CoQ, which is a key step in the process, because its product is the first intermediate that will be modified in the head by the next components of the synthesis process. Mutations in this protein have been linked to primary CoQ deficiency in humans, a rare disease predominantly affecting organs with a high energy demand. The reaction catalyzed by COQ2 and its mechanism are still unknown. Here, we aimed at clarifying the COQ2 reaction by exploring possible substrate binding sites using a strategy based on homology, comprising the identification of available ligand-bound homologs with solved structures in the Protein Data Bank (PDB) and their subsequent structural superposition in the AlphaFold predicted model for COQ2. The results highlight some residues located on the central cavity or the matrix loops that may be involved in substrate interaction, some of which are mutated in primary CoQ deficiency patients. Furthermore, we analyze the structural modifications introduced by the pathogenic mutations found in humans. These findings shed new light on the understanding of COQ2's function and, thus, CoQ's biosynthesis and the pathogenicity of primary CoQ deficiency.
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- 2024
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30. Toward Consensus Epitopes B and T of Tropomyosin Involved in Cross-Reactivity across Diverse Allergens: An In Silico Study.
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Martínez D, Fang L, Meza-Torres C, Garavito G, López-Lluch G, and Egea E
- Abstract
Tropomyosin (TM) is a pan-allergen with cross-reactivity to arthropods, insects, and nematodes in tropical regions. While IgE epitopes of TM contribute to sensitization, T-cell (MHC-II) epitopes polarize the Th2 immune response. This study aimed to identify linear B and T consensus epitopes among house dust mites, cockroaches, Ascaris lumbricoides , shrimp, and mosquitoes, exploring the molecular basis of cross-reactivity in allergic diseases. Amino acid sequences of Der p 10, Der f 10, Blo t 10, Lit v 1, Pen a 1, Pen m 1, rAsc l 3, Per a 7, Bla g 7, and Aed a 10 were collected from Allergen Nomenclature and UniProt. B epitopes were predicted using AlgPred 2.0 and BepiPred 3.0. T epitopes were predicted with NetMHCIIpan 4.1 against 10 HLA-II alleles. Consensus epitopes were obtained through analysis and Epitope Cluster Analysis in the Immune Epitope Database. We found 7 B-cell epitopes and 28 linear T-cell epitopes binding to MHC II. A unique peptide (residues 160-174) exhibited overlap between linear B-cell and T-cell epitopes, highly conserved across tropomyosin sequences. These findings shed light on IgE cross-reactivity among the tested species. The described immuno-informatics pipeline and epitopes can inform in vitro research and guide synthetic multi-epitope proteins' design for potential allergology immunotherapies. Further in silico studies are warranted to confirm epitope accuracy and guide future experimental protocols.
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- 2024
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31. The Evolution of Physical Performance throughout an Entire Season in Female Football Players.
- Author
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Reyes-Laredo F, Pareja-Blanco F, López-Lluch G, and Rodríguez-Bies E
- Abstract
Research on the evolution of performance throughout a season in team sports is scarce and mainly focused on men's teams. Our aim in this study was to examine the seasonal variations in relevant indices of physical performance in female football players. Twenty-seven female football players were assessed at week 2 of the season (preseason, PS), week 7 (end of preseason, EP), week 24 (half-season, HS), and week 38 (end of season, ES). Similar to the most common used conditioning tests in football, testing sessions consisted of (1) vertical countermovement jump (CMJ); (2) 20 m running sprint (T20); (3) 25 m side-step cutting maneuver test (V-CUT); and (4) progressive loading test in the full-squat exercise (V1-LOAD). Participants followed their normal football training procedure, which consisted of three weekly training sessions and an official match, without any type of intervention. No significant time effects were observed for CMJ height ( p = 0.29) and T20 ( p = 0.11) throughout the season. However, significant time effects were found for V-CUT ( p = 0.004) and V1-LOAD ( p = 0.001). V-CUT performance significantly improved from HS to ES ( p = 0.001). Significant increases were observed for V1-LOAD throughout the season: PS-HS ( p = 0.009); PS-ES ( p < 0.001); EP-ES ( p < 0.001); and HS-ES ( p = 0.009). These findings suggest that, over the course of the season, female football players experience an enhancement in muscle strength and change of direction ability. However, no discernible improvements were noted in sprinting and jumping capabilities during the same period.
- Published
- 2024
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32. Mountain spa rehabilitation improved health of patients with post-COVID-19 syndrome: pilot study.
- Author
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Gvozdjáková A, Sumbalová Z, Kucharská J, Rausová Z, Kovalčíková E, Takácsová T, Navas P, López-Lluch G, Mojto V, and Palacka P
- Subjects
- Humans, Pilot Projects, Post-Acute COVID-19 Syndrome, Mitochondria, Energy Metabolism, COVID-19
- Abstract
European Association of Spa Rehabilitation (ESPA) recommends spa rehabilitation for patients with post-COVID-19 syndrome. We tested the hypothesis that a high-altitude environment with clean air and targeted spa rehabilitation (MR - mountain spa rehabilitation) can contribute to the improving platelet mitochondrial bioenergetics, to accelerating patient health and to the reducing socioeconomic problems. Fifteen healthy volunteers and fourteen patients with post-COVID-19 syndrome were included in the study. All parameters were determined before MR (MR1) and 16-18 days after MR (MR2). Platelet mitochondrial respiration and OXPHOS were evaluated using high resolution respirometry method, coenzyme Q
10 level was determined by HPLC, and concentration of thiobarbituric acid reactive substances (TBARS) as a parameter of lipid peroxidation was determined spectrophotometrically. This pilot study showed significant improvement of clinical symptoms, lungs function, and regeneration of reduced CI-linked platelet mitochondrial respiration after MR in patients with post-COVID-19 syndrome. High-altitude environment with spa rehabilitation can be recommended for the acceleration of recovery of patients with post-COVID-19 syndrome., (© 2022. The Author(s).)- Published
- 2023
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33. Coenzyme Q10 Levels Associated With Cognitive Functioning and Executive Function in Older Adults.
- Author
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Fernández-Portero C, Amián JG, Bella R, López-Lluch G, and Alarcón D
- Subjects
- Humans, Female, Aged, Male, Cognition, Antioxidants, Oxidative Stress, Executive Function, Ubiquinone
- Abstract
Brain deterioration with age is associated with inflammation and oxidative stress that result in structural and functional changes. Recent studies have indicated that coenzyme Q10 (CoQ10) is associated with neurological oxidative stress and cognitive impairment. Studies with older people have shown a relationship between neurodegenerative diseases and CoQ10 levels. However, no studies have analyzed the relationship between CoQ10 and cognitive functioning in older adults. The aim of this study was to analyze the association between CoQ10 and cognitive functioning in an older adult sample, controlling for other factors that may influence aging, such as the level of physical activity and nutritional status. The sample consisted of 64 older adults aged 65-99 years (76.67 ± 8.16 years), among whom 48 were women (75%). The participants were recruited among those who attended community centers to voluntarily participate in leisure activities. According to previous studies, physical activity and nutritional status are positively associated with cognitive functioning. However, the main finding of this study was that plasma CoQ10, controlling for other measures, was significantly associated with cognitive functioning and executive function. The current findings suggest that a decline in cognitive capacities may be related to reduced antioxidant defenses, as reflected by low CoQ10 levels in older adults., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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34. Coenzyme Q-related compounds to maintain healthy mitochondria during aging.
- Author
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López-Lluch G
- Subjects
- Autophagy, Mitomycin, Ubiquinone pharmacology, Mitochondria
- Abstract
Mitochondrial dysfunction is one of the main factors that affects aging progression and many age-related diseases. Accumulation of dysfunctional mitochondria can be driven by unbalanced mito/autophagy or by decrease in mitochondrial biosynthesis and turnover. Coenzyme Q is an essential component of the mitochondrial electron transport chain and a key factor in the protection of membrane and mitochondrial DNA against oxidation. Coenzyme Q levels decay during aging and this can be considered an accelerating factor in mitochondrial dysfunction and aging progression. Supplementation with coenzyme Q is successful for some tissues and organs but not for others. For this reason, the role of coenzyme Q in systemic aging is a complex picture that needs different strategies depending on the organ considered the main objective to be addressed. In this chapter we focus on the different effects of coenzyme Q and related compounds and the probable strategies to induce endogenous synthesis to maintain healthy aging., (Copyright © 2023. Published by Elsevier Inc.)
- Published
- 2023
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35. Calorie Restriction Rescues Mitochondrial Dysfunction in Adck2-Deficient Skeletal Muscle.
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Hernández-Camacho JD, Fernández-Ayala DJM, Vicente-García C, Navas-Enamorado I, López-Lluch G, Oliva C, Artuch R, Garcia-Villoria J, Ribes A, de Cabo R, Carvajal JJ, and Navas P
- Abstract
ADCK2 haploinsufficiency-mediated mitochondrial coenzyme Q deficiency in skeletal muscle causes mitochondrial myopathy associated with defects in beta-oxidation of fatty acids, aged-matched metabolic reprogramming, and defective physical performance. Calorie restriction has proven to increase lifespan and delay the onset of chronic diseases associated to aging. To study the possible treatment by food deprivation, heterozygous Adck2 knockout mice were fed under 40% calorie restriction (CR) and the phenotype was followed for 7 months. The overall glucose and fatty acids metabolism in muscle was restored in mutant mice to WT levels after CR. CR modulated the skeletal muscle metabolic profile of mutant mice, partially rescuing the profile of WT animals. The analysis of mitochondria isolated from skeletal muscle demonstrated that CR increased both CoQ levels and oxygen consumption rate (OCR) based on both glucose and fatty acids substrates, along with mitochondrial mass. The elevated aerobic metabolism fits with an increase of type IIa fibers, and a reduction of type IIx in mutant muscles, reaching WT levels. To further explore the effect of CR over muscle stem cells, satellite cells were isolated and induced to differentiate in culture media containing serum from animals in either ad libitum or CR diets for 72 h. Mutant cells showed slower differentiation alongside with decreased oxygen consumption. In vitro differentiation of mutant cells was increased under CR serum reaching levels of WT isolated cells, recovering respiration measured by OCR and partially beta-oxidation of fatty acids. The overall increase of skeletal muscle bioenergetics following CR intervention is paralleled with a physical activity improvement, with some increases in two and four limbs strength tests, and weights strength test. Running wheel activity was also partially improved in mutant mice under CR. These results demonstrate that CR intervention, which has been shown to improve age-associated physical and metabolic decline in WT mice, also recovers the defective aerobic metabolism and differentiation of skeletal muscle in mice caused by ADCK2 haploinsufficiency., Competing Interests: IN-E is employed by Atsena Therapeutics, Durham, NC, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hernández-Camacho, Fernández-Ayala, Vicente-García, Navas-Enamorado, López-Lluch, Oliva, Artuch, Garcia-Villoria, Ribes, de Cabo, Carvajal and Navas.)
- Published
- 2022
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36. High coenzyme Q10 plasma levels improve stress and damage markers in professional soccer players during competition.
- Author
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Sánchez-Cuesta A, Cortés-Rodríguez AB, Navas-Enamorado I, Lekue JA, Viar T, Axpe M, Navas P, and López-Lluch G
- Subjects
- Antioxidants, Athletes, Biomarkers, Creatine Kinase, Humans, Hydrocortisone, Oxidative Stress, Soccer physiology, Ubiquinone analogs & derivatives, Ubiquinone blood
- Abstract
Ubiquinol, the reduced form of Coenzyme Q
10 (CoQ10 ), is a key factor in bioenergetics and antioxidant protection. During competition, professional soccer players suffer from considerable physical stress causing high risk of muscle damage. For athletes, supplementation with several antioxidants, including CoQ10 , is widely recommended to avoid oxidative stress and muscle damage. We performed an observational study of plasma parameters associated with CoQ10 levels in professional soccer players of the Spanish First League team Athletic Club de Bilbao over two consecutive seasons (n = 24-25) in order determine their relationship with damage, stress and performance during competition. We analyzed three different moments of the competition: preterm, initial phase and mid phase. Metabolites and factors related with stress (testosterone/cortisol) and muscle damage (creatine kinase) were determined. Physical activity during matches was analyzed over the 2015/16 season in those players participating in complete matches. In the mid phase of competition, CoQ10 levels were higher in 2015/16 (906.8 ± 307.9 vs. 584.3 ± 196.3 pmol/mL, p = 0.0006) High levels of CoQ10 in the hardest phase of competition were associated with a reduction in the levels of the muscle-damage marker creatine kinase (Pearsons' correlation coefficient (r) = - 0.460, p = 0.00168) and a trend for the stress marker cortisol (r = -0.252, p = 0.150). Plasma ubiquinol was also associated with better kidney function (r = -0.287, p = 0.0443 for uric acid). Furthermore, high CoQ10 levels were associated with higher muscle performance during matches. Our results suggest that high levels of plasma CoQ10 can prevent muscle damage, improve kidney function and are associated with higher performance in professional soccer players during competition.- Published
- 2022
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37. Cardiac fibroblasts display endurance to ischemia, high ROS control and elevated respiration regulated by the JAK2/STAT pathway.
- Author
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Beà A, Valero JG, Irazoki A, Lana C, López-Lluch G, Portero-Otín M, Pérez-Galán P, Inserte J, Ruiz-Meana M, Zorzano A, Llovera M, and Sanchis D
- Subjects
- Animals, Fibroblasts metabolism, Ischemia, Proto-Oncogene Proteins c-bcl-2 metabolism, Rats, Reactive Oxygen Species metabolism, Respiration, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Signal Transduction, Antioxidants, Janus Kinase 2 genetics, Janus Kinase 2 metabolism
- Abstract
Cardiovascular 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., (© 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2022
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38. Levels of Plasma Coenzyme Q 10 Are Associated with Physical Capacity and Cardiovascular Risk in the Elderly.
- Author
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de la Bella-Garzón R, Fernández-Portero C, Alarcón D, Amián JG, and López-Lluch G
- Abstract
Coenzyme Q
10 (CoQ10 ) is an essential factor for mitochondrial activity and antioxidant protection of cells, tissues and plasma lipoproteins. Its deficiency has been associated with aging progression in animals and humans. To determine if CoQ10 levels in plasma can be associated with frailty in elderly people (aged > 65), we studied the relationship of CoQ10 levels in blood with other parameters in plasma and with the physical activity and capacity in aged people. Our results indicate that high CoQ10 levels are directly associated with lower cardiovascular risk measured by the quotient total cholesterol/HDL cholesterol. Furthermore, high CoQ10 levels were found in people showing higher physical activity, stronger muscle capacity. CoQ10 also showed a strong inverse relationship with sedentarism and the up and go test, which is considered to be a frailty index. Interestingly, we found gender differences, indicating stronger correlations in women than in men. The importance of the maintenance of CoQ10 levels in elderly people to avoid sarcopenia and frailty in elderly people is discussed.- Published
- 2022
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39. Coenzyme Q at the Hinge of Health and Metabolic Diseases.
- Author
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Hernández-Camacho JD, García-Corzo L, Fernández-Ayala DJM, Navas P, and López-Lluch G
- Abstract
Coenzyme Q is a unique lipidic molecule highly conserved in evolution and essential to maintaining aerobic metabolism. It is endogenously synthesized in all cells by a very complex pathway involving a group of nuclear genes that share high homology among species. This pathway is tightly regulated at transcription and translation, but also by environment and energy requirements. Here, we review how coenzyme Q reacts within mitochondria to promote ATP synthesis and also integrates a plethora of metabolic pathways and regulates mitochondrial oxidative stress. Coenzyme Q is also located in all cellular membranes and plasma lipoproteins in which it exerts antioxidant function, and its reaction with different extramitochondrial oxidoreductases contributes to regulate the cellular redox homeostasis and cytosolic oxidative stress, providing a key factor in controlling various apoptosis mechanisms. Coenzyme Q levels can be decreased in humans by defects in the biosynthesis pathway or by mitochondrial or cytosolic dysfunctions, leading to a highly heterogeneous group of mitochondrial diseases included in the coenzyme Q deficiency syndrome. We also review the importance of coenzyme Q levels and its reactions involved in aging and age-associated metabolic disorders, and how the strategy of its supplementation has had benefits for combating these diseases and for physical performance in aging.
- Published
- 2021
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40. Cellular Models for Primary CoQ Deficiency Pathogenesis Study.
- Author
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Santos-Ocaña C, Cascajo MV, Alcázar-Fabra M, Staiano C, López-Lluch G, Brea-Calvo G, and Navas P
- Subjects
- Ataxia diagnosis, Exome genetics, Genome genetics, High-Throughput Nucleotide Sequencing, Humans, Mitochondrial Diseases diagnosis, Muscle Weakness diagnosis, Ubiquinone analysis, Ubiquinone biosynthesis, Ubiquinone genetics, Exome Sequencing, Whole Genome Sequencing, Ataxia genetics, Ataxia pathology, Mitochondria metabolism, Mitochondrial Diseases genetics, Mitochondrial Diseases pathology, Muscle Weakness genetics, Muscle Weakness pathology, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism, Ubiquinone analogs & derivatives, Ubiquinone deficiency
- Abstract
Primary coenzyme Q
10 (CoQ) deficiency includes a heterogeneous group of mitochondrial diseases characterized by low mitochondrial levels of CoQ due to decreased endogenous biosynthesis rate. These diseases respond to CoQ treatment mainly at the early stages of the disease. The advances in the next generation sequencing (NGS) as whole-exome sequencing (WES) and whole-genome sequencing (WGS) have increased the discoveries of mutations in either gene already described to participate in CoQ biosynthesis or new genes also involved in this pathway. However, these technologies usually provide many mutations in genes whose pathogenic effect must be validated. To functionally validate the impact of gene variations in the disease's onset and progression, different cell models are commonly used. We review here the use of yeast strains for functional complementation of human genes, dermal skin fibroblasts from patients as an excellent tool to demonstrate the biochemical and genetic mechanisms of these diseases and the development of human-induced pluripotent stem cells (hiPSCs) and iPSC-derived organoids for the study of the pathogenesis and treatment approaches.- Published
- 2021
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41. Secondary CoQ 10 deficiency, bioenergetics unbalance in disease and aging.
- Author
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Navas P, Cascajo MV, Alcázar-Fabra M, Hernández-Camacho JD, Sánchez-Cuesta A, Rodríguez ABC, Ballesteros-Simarro M, Arroyo-Luque A, Rodríguez-Aguilera JC, Fernández-Ayala DJM, Brea-Calvo G, López-Lluch G, and Santos-Ocaña C
- Subjects
- Aging metabolism, Alkyl and Aryl Transferases metabolism, Animals, Ataxia metabolism, Ataxia pathology, Energy Metabolism genetics, GTP Phosphohydrolases metabolism, Gene Expression Regulation, Humans, Mitochondria metabolism, Mitochondria pathology, Mitochondrial Diseases metabolism, Mitochondrial Diseases pathology, Mitochondrial Proteins metabolism, Muscle Weakness metabolism, Muscle Weakness pathology, Mutation, Niemann-Pick C1 Protein genetics, Niemann-Pick C1 Protein metabolism, Niemann-Pick Disease, Type C metabolism, Niemann-Pick Disease, Type C pathology, Signal Transduction, Ubiquinone genetics, Ubiquinone metabolism, Aging genetics, Alkyl and Aryl Transferases genetics, Ataxia genetics, GTP Phosphohydrolases genetics, Mitochondria genetics, Mitochondrial Diseases genetics, Mitochondrial Proteins genetics, Muscle Weakness genetics, Niemann-Pick Disease, Type C genetics, Ubiquinone analogs & derivatives, Ubiquinone deficiency
- Abstract
Coenzyme Q
10 (CoQ10 ) deficiency is a rare disease characterized by a decreased accumulation of CoQ10 in cell membranes. Considering that CoQ10 synthesis and most of its functions are carried out in mitochondria, CoQ10 deficiency cases are usually considered a mitochondrial disease. A relevant feature of CoQ10 deficiency is that it is the only mitochondrial disease with a successful therapy available, the CoQ10 supplementation. Defects in components of the synthesis machinery caused by mutations in COQ genes generate the primary deficiency of CoQ10 . Mutations in genes that are not directly related to the synthesis machinery cause secondary deficiency. Cases of CoQ10 deficiency without genetic origin are also considered a secondary deficiency. Both types of deficiency can lead to similar clinical manifestations, but the knowledge about primary deficiency is deeper than secondary. However, secondary deficiency cases may be underestimated since many of their clinical manifestations are shared with other pathologies. This review shows the current state of secondary CoQ10 deficiency, which could be even more relevant than primary deficiency for clinical activity. The analysis covers the fundamental features of CoQ10 deficiency, which are necessary to understand the biological and clinical differences between primary and secondary CoQ10 deficiencies. Further, a more in-depth analysis of CoQ10 secondary deficiency was undertaken to consider its origins, introduce a new way of classification, and include aging as a form of secondary deficiency., (© 2021 International Union of Biochemistry and Molecular Biology.)- Published
- 2021
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42. Coenzyme Q homeostasis in aging: Response to non-genetic interventions.
- Author
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López-Lluch G
- Subjects
- Antioxidants, Homeostasis, Mitochondria genetics, Ubiquinone
- Abstract
Coenzyme Q (CoQ) is a key component for many essential metabolic and antioxidant activities in cells in mitochondria and cell membranes. Mitochondrial dysfunction is one of the hallmarks of aging and age-related diseases. Deprivation of CoQ during aging can be the cause or the consequence of this mitochondrial dysfunction. In any case, it seems clear that aging-associated CoQ deprivation accelerates mitochondrial dysfunction in these diseases. Non-genetic prolongevity interventions, including CoQ dietary supplementation, can increase CoQ levels in mitochondria and cell membranes improving mitochondrial activity and delaying cell and tissue deterioration by oxidative damage. In this review, we discuss the importance of CoQ deprivation in aging and age-related diseases and the effect of prolongevity interventions on CoQ levels and synthesis and CoQ-dependent antioxidant activities., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
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43. Age-related mitochondrial dysfunction as a key factor in COVID-19 disease.
- Author
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Moreno Fernández-Ayala DJ, Navas P, and López-Lluch G
- Subjects
- Animals, COVID-19 immunology, COVID-19 mortality, Cytokine Release Syndrome etiology, Humans, Inflammation immunology, Inflammation physiopathology, Ubiquinone analogs & derivatives, Ubiquinone pharmacology, Aging immunology, COVID-19 complications, Mitochondria physiology, SARS-CoV-2
- Abstract
SARS-CoV-2 causes a severe pneumonia (COVID-19) that affects essentially elderly people. In COVID-19, macrophage infiltration into the lung causes a rapid and intense cytokine storm leading finally to a multi-organ failure and death. Comorbidities such as metabolic syndrome, obesity, type 2 diabetes, lung and cardiovascular diseases, all of them age-associated diseases, increase the severity and lethality of COVID-19. Mitochondrial dysfunction is one of the hallmarks of aging and COVID-19 risk factors. Dysfunctional mitochondria is associated with defective immunological response to viral infections and chronic inflammation. This review discuss how mitochondrial dysfunction is associated with defective immune response in aging and different age-related diseases, and with many of the comorbidities associated with poor prognosis in the progression of COVID-19. We suggest here that chronic inflammation caused by mitochondrial dysfunction is responsible of the explosive release of inflammatory cytokines causing severe pneumonia, multi-organ failure and finally death in COVID-19 patients. Preventive treatments based on therapies improving mitochondrial turnover, dynamics and activity would be essential to protect against COVID-19 severity., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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44. Physiopathology of Lifestyle Interventions in Non-Alcoholic Fatty Liver Disease (NAFLD).
- Author
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Carneros D, López-Lluch G, and Bustos M
- Subjects
- Humans, Weight Loss, Diet, Reducing, Exercise physiology, Life Style, Non-alcoholic Fatty Liver Disease therapy
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years. Diet and exercise interventions are the first-line treatment options, with weight loss via a hypocaloric diet being the most important therapeutic target in NAFLD. However, most NAFLD patients are not able to achieve such weight loss. Therefore, the requisite is the investigation of other effective therapeutic approaches. This review summarizes research on understanding complex pathophysiology underlying dietary approaches and exercise interventions with the potential to prevent and treat NAFLD.
- Published
- 2020
- Full Text
- View/download PDF
45. Involvement of the mitochondrial nuclease EndoG in the regulation of cell proliferation through the control of reactive oxygen species.
- Author
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Blasco N, Beà A, Barés G, Girón C, Navaridas R, Irazoki A, López-Lluch G, Zorzano A, Dolcet X, Llovera M, and Sanchis D
- Subjects
- Animals, Cell Cycle, Glycogen Synthase Kinase 3 beta, HEK293 Cells, Humans, Mice, Rats, Apoptosis, Cell Proliferation, Endodeoxyribonucleases, Mitochondria, Reactive Oxygen Species
- Abstract
The apoptotic nuclease EndoG is involved in mitochondrial DNA replication. Previous results suggested that, in addition to regulate cardiomyocyte hypertrophy, EndoG could be involved in cell proliferation. Here, by using in vivo and cell culture models, we investigated the role of EndoG in cell proliferation. Genetic deletion of Endog both in vivo and in cultured cells or Endog silencing in vitro induced a defect in rodent and human cell proliferation with a tendency of cells to accumulate in the G
1 phase of cell cycle and increased reactive oxygen species (ROS) production. The defect in cell proliferation occurred with a decrease in the activity of the AKT/PKB-GSK-3β-Cyclin D axis and was reversed by addition of ROS scavengers. EndoG deficiency did not affect the expression of ROS detoxifying enzymes, nor the expression of the electron transport chain complexes and oxygen consumption rate. Addition of the micropeptide Humanin to EndoG-deficient cells restored AKT phosphorylation and proliferation without lowering ROS levels. Thus, our results show that EndoG is important for cell proliferation through the control of ROS and that Humanin can restore cell division in EndoG-deficient cells and counteracts the effects of ROS on AKT phosphorylation., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)- Published
- 2020
- Full Text
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46. Resveratrol Regulates the Expression of Genes Involved in CoQ Synthesis in Liver in Mice Fed with High Fat Diet.
- Author
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Meza-Torres C, Hernández-Camacho JD, Cortés-Rodríguez AB, Fang L, Bui Thanh T, Rodríguez-Bies E, Navas P, and López-Lluch G
- Abstract
Resveratrol (RSV) is a bioactive natural molecule that induces antioxidant activity and increases protection against oxidative damage. RSV could be used to mitigate damages associated to metabolic diseases and aging. Particularly, RSV regulates different aspects of mitochondrial metabolism. However, no information is available about the effects of RSV on Coenzyme Q (CoQ), a central component in the mitochondrial electron transport chain. Here, we report for the first time that RSV modulates COQ genes and parameters associated to metabolic syndrome in mice. Mice fed with high fat diet (HFD) presented a higher weight gain, triglycerides (TGs) and cholesterol levels while RSV reverted TGs to control level but not weight or cholesterol. HFD induced a decrease of COQs gene mRNA level, whereas RSV reversed this decrease in most of the COQs genes. However, RSV did not show effect on CoQ
9 , CoQ10 and total CoQ levels, neither in CoQ-dependent antioxidant enzymes. HFD influenced mitochondrial dynamics and mitophagy markers. RSV modulated the levels of PINK1 and PARKIN and their ratio, indicating modulation of mitophagy. In summary, we report that RSV influences some of the metabolic adaptations of HFD affecting mitochondrial physiology while also regulates COQs gene expression levels in a process that can be associated with mitochondrial dynamics and turnover.- Published
- 2020
- Full Text
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47. The Important Role of CoQ 10 in Aging.
- Author
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López-Lluch G
- Abstract
Coenzyme Q
10 ( CoQ10 ) is an essential lipid present in all cell membranes[...]., Competing Interests: The authors declare no conflict of interest.- Published
- 2019
- Full Text
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48. ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.
- Author
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Vázquez-Fonseca L, Schaefer J, Navas-Enamorado I, Santos-Ocaña C, Hernández-Camacho JD, Guerra I, Cascajo MV, Sánchez-Cuesta A, Horvath Z, Siendones E, Jou C, Casado M, Gutiérrez P, Brea-Calvo G, López-Lluch G, Fernández-Ayala DJM, Cortés-Rodríguez AB, Rodríguez-Aguilera JC, Matté C, Ribes A, Prieto-Soler SY, Dominguez-Del-Toro E, Francesco AD, Aon MA, Bernier M, Salviati L, Artuch R, Cabo R, Jackson S, and Navas P
- Abstract
Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2 , a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data showed that A dck 2 +/- mice exhibited impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in Coenzyme Q (CoQ) biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation., Competing Interests: The authors declare no competing financial interest.
- Published
- 2019
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49. The Impact of Aging, Calorie Restriction and Dietary Fat on Autophagy Markers and Mitochondrial Ultrastructure and Dynamics in Mouse Skeletal Muscle.
- Author
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Gutiérrez-Casado E, Khraiwesh H, López-Domínguez JA, Montero-Guisado J, López-Lluch G, Navas P, de Cabo R, Ramsey JJ, González-Reyes JA, and Villalba JM
- Subjects
- Animals, Autophagy, Beclin-1 metabolism, Biomarkers metabolism, Dynamins metabolism, Fish Oils administration & dosage, GTP Phosphohydrolases metabolism, Longevity, Mice, Inbred C57BL, Microscopy, Electron, Transmission, Microtubule-Associated Proteins metabolism, Models, Animal, Muscle Fibers, Skeletal ultrastructure, Protein Kinases metabolism, RNA-Binding Proteins metabolism, Sarcopenia metabolism, Soybean Oil administration & dosage, Ubiquitin-Protein Ligases metabolism, Aging metabolism, Caloric Restriction, Dietary Fats administration & dosage, Mitochondria, Muscle metabolism, Mitochondria, Muscle ultrastructure
- Abstract
Loss of skeletal muscle mass and function is a hallmark of aging. This phenomenon has been related to a dysregulation of mitochondrial function and proteostasis. Calorie restriction (CR) has been demonstrated to delay aging and preserve function until late in life, particularly in muscle. Recently, we reported the type of dietary fat plays an important role in determining life span extension with 40% CR in male mice. In these conditions, lard fed mice showed an increased longevity compared to mice fed soybean or fish oils. In this article, we analyze the effect of 40% CR on muscle mitochondrial mass, autophagy, and mitochondrial dynamics markers in mice fed these diets. In CR fed animals, lard preserved muscle fibers structure, mitochondrial ultrastructure, and fission/fusion dynamics and autophagy, not only compared to control animals, but also compared with CR mice fed soybean and fish oils as dietary fat. We focus our discussion on dietary fatty acid saturation degree as an essential predictor of life span extension in CR mice., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
- Full Text
- View/download PDF
50. Bioavailability of coenzyme Q10 supplements depends on carrier lipids and solubilization.
- Author
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López-Lluch G, Del Pozo-Cruz J, Sánchez-Cuesta A, Cortés-Rodríguez AB, and Navas P
- Subjects
- Administration, Oral, Adolescent, Adult, Area Under Curve, Biological Availability, Capsules, Cross-Over Studies, Double-Blind Method, Female, Humans, Male, Solubility, Ubiquinone analogs & derivatives, Ubiquinone chemistry, Ubiquinone pharmacokinetics, Young Adult, Dietary Supplements, Drug Carriers, Lipids, Ubiquinone administration & dosage
- Abstract
Objectives: Bioavailability of supplements with coenzyme Q10 (CoQ
10 ) in humans seems to depend on the excipients of formulations and on physiological characteristics of the individuals. The aim of this study was to determine which factors presented in CoQ10 supplements affect the different response to CoQ10 in humans., Methods: We tested seven different supplement formulations containing 100 mg of CoQ10 in 14 young, healthy individuals. Bioavailability was measured as area under the curve of plasma CoQ10 levels over 48 h after ingestion of a single dose. Measurements were repeated in the same group of 14 volunteers in a double-blind crossover design with a minimum of 4 wk washout between intakes., Results: Bioavailability of the formulations showed large differences that were statistically significant. The two best absorbable formulations were soft-gel capsules containing ubiquinone (oxidized CoQ10 ) or ubiquinol (reduced CoQ10 ). The matrix used to dissolve CoQ10 and the proportion and addition of preservatives such as vitamin C affected the bioavailability of CoQ10 . Although control measurements documented that all formulations contained 100 mg of either CoQ10 or ubiquinol, some of the participants showed high and others lower capacity to reach high increase of CoQ10 in blood, indicating the participation of individual unknown physiological factors., Conclusion: This study highlights the importance of individually adapted selection of best formulations to reach the highest bioavailability of CoQ10 in humans., (Copyright © 2019 Elsevier Ltd. All rights reserved.)- Published
- 2019
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