Testosterone Plus Low-Intensity Physical Training in Late Life Improves Functional Performance, Skeletal Muscle Mitochondrial Biogenesis, and Mitochondrial Quality Control in Male Mice
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{"title"=>"Testosterone Plus Low-Intensity Physical Training in Late Life Improves Functional Performance, Skeletal Muscle Mitochondrial Biogenesis, and Mitochondrial Quality Control in Male Mice", "type"=>"journal", "authors"=>[{"first_name"=>"Wen", "last_name"=>"Guo", "scopus_author_id"=>"55808101400"}, {"first_name"=>"Siu", "last_name"=>"Wong", "scopus_author_id"=>"16231842300"}, {"first_name"=>"Michelle", "last_name"=>"Li", "scopus_author_id"=>"36701697500"}, {"first_name"=>"Wentao", "last_name"=>"Liang", "scopus_author_id"=>"55523124600"}, {"first_name"=>"Marc", "last_name"=>"Liesa", "scopus_author_id"=>"8578548700"}, {"first_name"=>"Carlo", "last_name"=>"Serra", "scopus_author_id"=>"55439738900"}, {"first_name"=>"Ravi", "last_name"=>"Jasuja", "scopus_author_id"=>"6603512208"}, {"first_name"=>"Andrzej", "last_name"=>"Bartke", "scopus_author_id"=>"36044638400"}, {"first_name"=>"James L.", "last_name"=>"Kirkland", "scopus_author_id"=>"35594558800"}, {"first_name"=>"Orian", "last_name"=>"Shirihai", "scopus_author_id"=>"6602891532"}, {"first_name"=>"Shalender", "last_name"=>"Bhasin", "scopus_author_id"=>"7102133629"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84871150088", "doi"=>"10.1371/journal.pone.0051180", "pui"=>"366273786", "pmid"=>"23240002", "scopus"=>"2-s2.0-84871150088", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)"}, "id"=>"3fb28ac8-2e0f-3833-82d0-ca9e13ee1edb", "abstract"=>"Testosterone supplementation increases muscle mass in older men but has not been shown to consistently improve physical function and activity. It has been hypothesized that physical exercise is required to induce the adaptations necessary for translation of testosterone-induced muscle mass gain into functional improvements. However, the effects of testosterone plus low intensity physical exercise training (T/PT) on functional performance and bioenergetics are unknown. In this pilot study, we tested the hypothesis that combined administration of T/PT would improve functional performance and bioenergetics in male mice late in life more than low-intensity physical training alone. 28-month old male mice were randomized to receive T/PT or vehicle plus physical training (V/PT) for 2 months. Compare to V/PT control, administration of T/PT was associated with improvements in muscle mass, grip strength, spontaneous physical movements, and respiratory activity. These changes were correlated with increased mitochondrial DNA copy number and expression of markers for mitochondrial biogenesis. Mice receiving T/PT also displayed increased expression of key elements for mitochondrial quality control, including markers for mitochondrial fission-and-fusion and mitophagy. Concurrently, mice receiving T/PT also displayed increased expression of markers for reduced tissue oxidative damage and improved muscle quality. Conclusion: Testosterone administered with low-intensity physical training improves grip strength, spontaneous movements, and respiratory activity. These functional improvements were associated with increased muscle mitochondrial biogenesis and improved mitochondrial quality control.", "link"=>"http://www.mendeley.com/research/testosterone-plus-lowintensity-physical-training-late-life-improves-functional-performance-skeletal-2", "reader_count"=>35, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>3, "Student > Master"=>5, "Other"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Nursing and Health Professions"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>12, "Design"=>1, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Sports and Recreations"=>3, "Chemistry"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Design"=>{"Design"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>12}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Sports and Recreations"=>{"Sports and Recreations"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Brazil"=>1, "Spain"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/528195"], "description"=>"<p>(<b>A</b>) Testosterone increased the mRNA expression of selected transcripts involved in mitochondrial fission, fusion, and mitophagy. (<b>B</b>) Testosterone increased the expression of mitochondrial fusion protein mitofusin 2 (MFN2) and mitochondrial fission protein DRP1; both are normalized to GAPDH. (<b>C</b>) Testosterone increased protein expression of autophagasome marker LC3II in whole tissue homogenates with a reciprocal decrease in the protein expression of autophagasome adaptor/substrate SQSMT1/p62. (<b>D</b>) Testosterone increased the expression of LC3II and Parkin in the mitochondria-enriched fraction of skeletal muscle lysate. Each lane represents one individual animal. The data in the bar graphs are mean ± SEM of desitometry results, and analyzed by <i>t</i> test. N = 5 for the control (C) group and 8 for the testosterone (T) group (for visual clarity, only five are displayed in Western blots).</p>", "links"=>[], "tags"=>["testosterone", "supplementation", "low-intensity", "mitochondrial", "skeletal"], "article_id"=>198676, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051180.g004", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_testosterone_supplementation_plus_low_intensity_physical_training_on_mitochondrial_quality_control_in_skeletal_muscle_/198676", "title"=>"Effect of testosterone supplementation plus low-intensity physical training on mitochondrial quality control in skeletal muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:24:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/528072"], "description"=>"<p>(<b>A</b>) (left panel) Western analysis of a panel of subunits of complex I-V as well as mitochondrial aconitase (ACO2) and superoxide dismutase (MnSOD). GAPDH was used as loading control and expression of androgen receptor was measured as a positive control; (right panel) quantification of protein expression normalized to GAPDH. (<b>B</b>). Activity of mitochondrial enzyme citrate synthase, complex I, and complex IV. All measurements were performed using whole tissue homogenates of the triceps muscle group. Bar graphs are presented as mean ± SEM and group means were compared using Student’s <i>t</i> test, N = 5 for the control (C) group and 8 for the testosterone (T) group.</p>", "links"=>[], "tags"=>["testosterone", "supplementation", "low-intensity", "mitochondrial", "proteins", "enzymes", "skeletal"], "article_id"=>198551, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051180.g003", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_testosterone_supplementation_plus_low_intensity_physical_training_on_the_expression_of_mitochondrial_proteins_and_the_activity_of_mitochondrial_marker_enzymes_in_skeletal_muscle_/198551", "title"=>"Effect of testosterone supplementation plus low-intensity physical training on the expression of mitochondrial proteins and the activity of mitochondrial marker enzymes in skeletal muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:22:31"}
  • {"files"=>["https://ndownloader.figshare.com/files/527780"], "description"=>"<p>(<b>A</b>) Forelimb grip strength measured at baseline (wk 0, N = 8 per group, C: control, T: testosterone) and after 7 weeks of (N = 6 for control, N = 8 for T group) testosterone supplementation (10 mg/kg, sc, twice per week). Control was injected with an equal volume of vehicle (0.1 ml). (<b>B</b>) Spontaneous physical movements recorded as total counts of infrared beam breaking per min. Each animal was housed individually in a metabolic cage. Results were averaged separately over the light and dark periods. The measurement was performed during week 6 after testosterone supplementation (N = 4 for each group). Xtot, Ytot, Ztot each denotes movements in X-axis, Y-axis, and Z-axis. (<b>C</b>) Mean respiratory activity recorded as oxygen consumption and carbon dioxide production for animals individually housed in a metabolic cage (N = 4). Results were normalized to total body weight. All results are shown as mean ± SEM, and the difference between control and testosterone groups at each time period was analyzed by <i>t</i> test. ns, not significantly different.</p>", "links"=>[], "tags"=>["testosterone", "supplementation", "low-intensity", "spontaneous", "respiratory"], "article_id"=>198265, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051180.g001", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_testosterone_supplementation_plus_low_intensity_physical_training_on_grip_strength_spontaneous_physical_activity_and_respiratory_activity_in_old_male_mice_/198265", "title"=>"Effect of testosterone supplementation plus low-intensity physical training on grip strength, spontaneous physical activity, and respiratory activity in old male mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:17:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/527960"], "description"=>"<p>(<b>A</b>) Testosterone increased mitochondrial DNA (mtDNA) copy number when normalized to nuclear genome DNA (nDNA). (<b>B</b>) Testosterone increased mtDNA-encoded mitochondrial transcripts for markers of complex I (NADH dehydrogenase subunits: ND1, ND4), complex III (cytochrome b: Cyto b), complex IV (cytochrome c oxidase subunits: Cox2a and Cox3a), and complex V (ATP synthase subunit 6, APT6) of the electron transport chain. (<b>C</b>) Testosterone increased the expression of selected nuclear genome-encoded mitochondrial transcripts for δ-aminolevulinate synthase 1 (ALAS1), adenine nucleotide translocator (ANT), Carnitine palmitoyltransferase 1(CPT1β, CPT1α). pyruvate dehydrogenase kinase 4 (PDK4), medium-chain acylCoA dehydrogenase (MCAD), uncoupling protein 3 (UCP3), and cytochrom c (Cyto c). All qPCR results were normalized to house-keeping gene Hypoxanthine phosphoribosyltransferase (HPRT) and expressed in an arbitrary unit (a.u). All results were obtained from triceps and presented as mean ± SEM and compared by <i>t</i> test. N = 5 for the control (C) and N = 8 for the testosterone (T) group.</p>", "links"=>[], "tags"=>["testosterone", "supplementation", "low-intensity", "markers", "mitochondrial", "biogenesis", "skeletal"], "article_id"=>198442, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051180.g002", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_testosterone_supplementation_plus_low_intensity_physical_training_on_markers_of_mitochondrial_biogenesis_in_the_skeletal_muscle_/198442", "title"=>"Effect of testosterone supplementation plus low-intensity physical training on markers of mitochondrial biogenesis in the skeletal muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/528296"], "description"=>"<p>(<b>A</b>) Testosterone reduced skeletal muscle thiobarbituric acid reactive substance (TBAR) in quadriceps (left) and gastrocnemius (right) muscle homogenates, implying a reduction in tissue oxidant stress. (<b>B</b>) Testosterone reduced phosphorylation of the two stress-activated protein kinase JNK2 and p38, without affecting the mitogen-activated Erk42/44; serving as a second line of evidence for a reduction in tissue stress in response to testosterone supplementation plus low-intensity physical training interventions. (<b>C</b>) Testosterone increased mRNA expression of IGF1 and FGF21 while reduced mRNA expression of MURF1 and MAFbx in skeletal muscle (triceps). The data in the bar graphs are mean ± SEM and analyzed by <i>t</i> test. N = 5 for the control (C) group and 8 for the testosterone (T) group (for visual clarity, only five are displayed for each group in the Western blots).</p>", "links"=>[], "tags"=>["testosterone", "supplementation", "low-intensity", "stress-activated", "kinases", "skeletal"], "article_id"=>198781, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0051180.g005", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_testosterone_supplementation_plus_low_intensity_physical_training_on_protein_oxidation_carbonylation_and_phosphorylation_activation_of_stress_activated_kinases_in_skeletal_muscle_/198781", "title"=>"Effect of testosterone supplementation plus low-intensity physical training on protein oxidation/carbonylation and phosphorylation/activation of stress-activated kinases in skeletal muscle.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-12-11 02:26:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/284431", "https://ndownloader.figshare.com/files/284496", "https://ndownloader.figshare.com/files/284565", "https://ndownloader.figshare.com/files/284617"], "description"=>"<div><p>Testosterone supplementation increases muscle mass in older men but has not been shown to consistently improve physical function and activity. It has been hypothesized that physical exercise is required to induce the adaptations necessary for translation of testosterone-induced muscle mass gain into functional improvements. However, the effects of testosterone plus low intensity physical exercise training (T/PT) on functional performance and bioenergetics are unknown. In this pilot study, we tested the hypothesis that combined administration of T/PT would improve functional performance and bioenergetics in male mice late in life more than low-intensity physical training alone. 28-month old male mice were randomized to receive T/PT or vehicle plus physical training (V/PT) for 2 months. Compare to V/PT control, administration of T/PT was associated with improvements in muscle mass, grip strength, spontaneous physical movements, and respiratory activity. These changes were correlated with increased mitochondrial DNA copy number and expression of markers for mitochondrial biogenesis. Mice receiving T/PT also displayed increased expression of key elements for mitochondrial quality control, including markers for mitochondrial fission-and-fusion and mitophagy. Concurrently, mice receiving T/PT also displayed increased expression of markers for reduced tissue oxidative damage and improved muscle quality. Conclusion: Testosterone administered with low-intensity physical training improves grip strength, spontaneous movements, and respiratory activity. These functional improvements were associated with increased muscle mitochondrial biogenesis and improved mitochondrial quality control.</p> </div>", "links"=>[], "tags"=>["testosterone", "low-intensity", "improves", "skeletal", "mitochondrial", "mice"], "article_id"=>116063, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Developmental Biology", "Evolutionary Biology"], "users"=>["Wen Guo", "Siu Wong", "Michelle Li", "Wentao Liang", "Marc Liesa", "Carlo Serra", "Ravi Jasuja", "Andrzej Bartke", "James L. Kirkland", "Orian Shirihai", "Shalender Bhasin"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0051180.s001", "https://dx.doi.org/10.1371/journal.pone.0051180.s002", "https://dx.doi.org/10.1371/journal.pone.0051180.s003", "https://dx.doi.org/10.1371/journal.pone.0051180.s004"], "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Testosterone_Plus_Low_Intensity_Physical_Training_in_Late_Life_Improves_Functional_Performance_Skeletal_Muscle_Mitochondrial_Biogenesis_and_Mitochondrial_Quality_Control_in_Male_Mice__/116063", "title"=>"Testosterone Plus Low-Intensity Physical Training in Late Life Improves Functional Performance, Skeletal Muscle Mitochondrial Biogenesis, and Mitochondrial Quality Control in Male Mice", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-12-11 01:41:03"}

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Relative Metric

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