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dc.contributor.author
Pereyra, Andrea Soledad  
dc.contributor.author
Wang, Zhong-Min  
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Messi, Maria Laura  
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Zhang, Tan  
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Wu, Hanzhi  
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Register, Thomas C.  
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Forbes, Elizabeth  
dc.contributor.author
Devarie Baez, Nelmi O.  
dc.contributor.author
Files, Daniel Clark  
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Abba, Martín Carlos  
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Furdui, Cristina  
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Delbono, Osvaldo  
dc.date.available
2018-06-15T14:58:01Z  
dc.date.issued
2017-08  
dc.identifier.citation
Pereyra, Andrea Soledad; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; et al.; BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice; Gerontological Soc Amer; Journals Of Gerontology Series A-biological Sciences And Medical Sciences; 72; 8; 8-2017; 1045-1053  
dc.identifier.issn
1079-5006  
dc.identifier.uri
http://hdl.handle.net/11336/48769  
dc.description.abstract
Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation- contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Gerontological Soc Amer  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Aging  
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Body Fat  
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Calpain  
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Sarcopenia  
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Skeletal Muscle  
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Inmunología  
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Medicina Básica  
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CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-06-13T14:19:01Z  
dc.journal.volume
72  
dc.journal.number
8  
dc.journal.pagination
1045-1053  
dc.journal.pais
Estados Unidos  
dc.journal.ciudad
Oxford  
dc.description.fil
Fil: Pereyra, Andrea Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata ; Argentina. Wake Forest School of Medicine; Estados Unidos  
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Fil: Wang, Zhong-Min. Wake Forest School of Medicine; Estados Unidos  
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Fil: Messi, Maria Laura. Wake Forest School of Medicine; Estados Unidos  
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Fil: Zhang, Tan. Wake Forest School of Medicine; Estados Unidos  
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Fil: Wu, Hanzhi. Wake Forest School of Medicine; Estados Unidos  
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Fil: Register, Thomas C.. Wake Forest School of Medicine; Estados Unidos  
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Fil: Forbes, Elizabeth. Wake Forest School of Medicine; Estados Unidos  
dc.description.fil
Fil: Devarie Baez, Nelmi O.. Wake Forest School of Medicine; Estados Unidos  
dc.description.fil
Fil: Files, Daniel Clark. Wake Forest School of Medicine; Estados Unidos  
dc.description.fil
Fil: Abba, Martín Carlos. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina  
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Fil: Furdui, Cristina. Wake Forest School of Medicine; Estados Unidos  
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Fil: Delbono, Osvaldo. Wake Forest School of Medicine; Estados Unidos  
dc.journal.title
Journals Of Gerontology Series A-biological Sciences And Medical Sciences  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.1093/gerona/glw192  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/biomedgerontology/article/72/8/1045/2328593