Resultados totales (Incluyendo duplicados): 33785
Encontrada(s) 3379 página(s)
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331821
Dataset. 2022

VIDEO2_ANALYSIS OF ACTOMYOSIN OSCILLATORY DYNAMICS USING A COARSE-GRAINED MODEL.MOV [DATASET]

  • Hernández del Valle, Miguel
  • Valencia-Expósito, Andrea
  • Gorfinkiel, Nicole
  • Martín-Bermudo, María D.
  • Míguez, David G.
Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331821
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331821
HANDLE: http://hdl.handle.net/10261/331821
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331821
PMID: http://hdl.handle.net/10261/331821
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331821
Ver en: http://hdl.handle.net/10261/331821
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331821

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331822
Dataset. 2022

ADDITIONAL FILE 1 OF INTEGRATING PATHWAY KNOWLEDGE WITH DEEP NEURAL NETWORKS TO REDUCE THE DIMENSIONALITY IN SINGLE-CELL RNA-SEQ DATA

  • Gundogdu, Pelin
  • Loucera, Carlos
  • Alamo-Alvarez, Inmaculada
  • Dopazo, Joaquín
  • Nepomuceno, Isabel
Additional file 1. Supplementary material for: Integrating pathway knowledge with deep neural networks to reduce the dimensionality in single-cell RNA-seq data., Ministerio de Ciencia e Innovación H2020 Marie Skłodowska-Curie Actions Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331822
HANDLE: http://hdl.handle.net/10261/331822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331822
PMID: http://hdl.handle.net/10261/331822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331822
Ver en: http://hdl.handle.net/10261/331822
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331822

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331825
Dataset. 2022

VIDEO3_ANALYSIS OF ACTOMYOSIN OSCILLATORY DYNAMICS USING A COARSE-GRAINED MODEL.AVI [DATASET]

  • Hernández del Valle, Miguel
  • Valencia-Expósito, Andrea
  • Gorfinkiel, Nicole
  • Martín-Bermudo, María D.
  • Míguez, David G.
Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331825
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331825
HANDLE: http://hdl.handle.net/10261/331825
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331825
PMID: http://hdl.handle.net/10261/331825
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331825
Ver en: http://hdl.handle.net/10261/331825
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331825

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331826
Dataset. 2022

VIDEO4_ANALYSIS OF ACTOMYOSIN OSCILLATORY DYNAMICS USING A COARSE-GRAINED MODEL.AVI [DATASET]

  • Hernández del Valle, Miguel
  • Valencia-Expósito, Andrea
  • Gorfinkiel, Nicole
  • Martín-Bermudo, María D.
  • Míguez, David G.
Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331826
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331826
HANDLE: http://hdl.handle.net/10261/331826
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331826
PMID: http://hdl.handle.net/10261/331826
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331826
Ver en: http://hdl.handle.net/10261/331826
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331826

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331827
Dataset. 2022

VIDEO5_ANALYSIS OF ACTOMYOSIN OSCILLATORY DYNAMICS USING A COARSE-GRAINED MODEL.AVI [DATASET]

  • Hernández del Valle, Miguel
  • Valencia-Expósito, Andrea
  • Gorfinkiel, Nicole
  • Martín-Bermudo, María D.
  • Míguez, David G.
Autonomous oscillatory dynamics are ubiquitous at every level in Biology. At the cellular level, one of the most relevant and well characterized examples of periodic behavior is the cyclic assembly and disassembly of actomyosin networks. In Drosophila, these oscillations induce the robust contraction and expansion of individual cells required for correct dorsal closure, while in the follicular epithelium that surrounds the germline, periodic contractions of the basal actomyosin network are required for proper elongation of the egg chamber. While some studies suggest that actomyosin oscillations are driven by upstream signaling or mechanochemical features, we have recently proposed that they arise as a systems property from the competition between two well characterized features of the actomyosin machinery: 1) cooperative assembly of actin networks mediated by Actin crosslinker proteins and 2) tension-induced disassembly of actin networks mediated by myosin motors. Here, we perform experiments in amnioserosa and in the follicle cells of drosophila and simulations using a coarse-grained model of the actomyosin cortex to characterize the properties of the oscillations and how they depend on different features of the system. We also compare model and experiments to study the dynamics of actomyosin flows and the effect of mechanical coupling between cells in the tissue. In conclusion, our model is a powerful tool to study key features of actomyosin oscillations, from the effect of the individual components to network properties and finally supra-cellular organization of the oscillations at the tissue level., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331827
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331827
HANDLE: http://hdl.handle.net/10261/331827
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331827
PMID: http://hdl.handle.net/10261/331827
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331827
Ver en: http://hdl.handle.net/10261/331827
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331827

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331828
Dataset. 2022

DATASHEET1_CALORIE RESTRICTION RESCUES MITOCHONDRIAL DYSFUNCTION IN ADCK2-DEFICIENT SKELETAL MUSCLE.DOCX

  • Hernández-Camacho, Juan Diego
  • Fernández-Ayala, Daniel J. M.
  • Vicente-García, Cristina
  • Navas-Enamorado, Ignacio
  • López-Lluch, Guillermo
  • Oliva, Clara
  • Artuch, Rafael
  • Garcia-Villoria, Judith
  • Ribes, Antonia
  • Cabo, Rafael de
  • Carvajal, Jaime J.
  • Navas, Plácido
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., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331828
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331828
HANDLE: http://hdl.handle.net/10261/331828
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331828
PMID: http://hdl.handle.net/10261/331828
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331828
Ver en: http://hdl.handle.net/10261/331828
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331828

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331829
Dataset. 2022

IMAGE1_CALORIE RESTRICTION RESCUES MITOCHONDRIAL DYSFUNCTION IN ADCK2-DEFICIENT SKELETAL MUSCLE.JPEG [DATASET]

  • Hernández-Camacho, Juan Diego
  • Fernández-Ayala, Daniel J. M.
  • Vicente-García, Cristina
  • Navas-Enamorado, Ignacio
  • López-Lluch, Guillermo
  • Oliva, Clara
  • Artuch, Rafael
  • Garcia-Villoria, Judith
  • Ribes, Antonia
  • Cabo, Rafael de
  • Carvajal, Jaime J.
  • Navas, Plácido
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., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331829
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331829
HANDLE: http://hdl.handle.net/10261/331829
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331829
PMID: http://hdl.handle.net/10261/331829
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331829
Ver en: http://hdl.handle.net/10261/331829
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331829

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331830
Dataset. 2022

IMAGE2_CALORIE RESTRICTION RESCUES MITOCHONDRIAL DYSFUNCTION IN ADCK2-DEFICIENT SKELETAL MUSCLE.JPEG [DATASET]

  • Hernández-Camacho, Juan Diego
  • Fernández-Ayala, Daniel J. M.
  • Vicente-García, Cristina
  • Navas-Enamorado, Ignacio
  • López-Lluch, Guillermo
  • Oliva, Clara
  • Artuch, Rafael
  • Garcia-Villoria, Judith
  • Ribes, Antonia
  • Cabo, Rafael de
  • Carvajal, Jaime J.
  • Navas, Plácido
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., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331830
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331830
HANDLE: http://hdl.handle.net/10261/331830
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331830
PMID: http://hdl.handle.net/10261/331830
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331830
Ver en: http://hdl.handle.net/10261/331830
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331830

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331831
Dataset. 2022

IMAGE3_CALORIE RESTRICTION RESCUES MITOCHONDRIAL DYSFUNCTION IN ADCK2-DEFICIENT SKELETAL MUSCLE.JPEG [DATASET]

  • Hernández-Camacho, Juan Diego
  • Fernández-Ayala, Daniel J. M.
  • Vicente-García, Cristina
  • Navas-Enamorado, Ignacio
  • López-Lluch, Guillermo
  • Oliva, Clara
  • Artuch, Rafael
  • Garcia-Villoria, Judith
  • Ribes, Antonia
  • Cabo, Rafael de
  • Carvajal, Jaime J.
  • Navas, Plácido
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., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331831
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331831
HANDLE: http://hdl.handle.net/10261/331831
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331831
PMID: http://hdl.handle.net/10261/331831
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331831
Ver en: http://hdl.handle.net/10261/331831
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331831

Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331832
Dataset. 2022

IMAGE4_CALORIE RESTRICTION RESCUES MITOCHONDRIAL DYSFUNCTION IN ADCK2-DEFICIENT SKELETAL MUSCLE.JPEG [DATASET]

  • Hernández-Camacho, Juan Diego
  • Fernández-Ayala, Daniel J. M.
  • Vicente-García, Cristina
  • Navas-Enamorado, Ignacio
  • López-Lluch, Guillermo
  • Oliva, Clara
  • Artuch, Rafael
  • Garcia-Villoria, Judith
  • Ribes, Antonia
  • Cabo, Rafael de
  • Carvajal, Jaime J.
  • Navas, Plácido
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., Peer reviewed

Proyecto: //
DOI: http://hdl.handle.net/10261/331832
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331832
HANDLE: http://hdl.handle.net/10261/331832
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331832
PMID: http://hdl.handle.net/10261/331832
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331832
Ver en: http://hdl.handle.net/10261/331832
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/331832

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