For striated muscles, functionality is defined as the capability of an organ, the heart or a muscle, or a cell, muscle fibers, to develop force and power during isometric, shortening, or lengthening contractions. Our working hypothesis is that functionality of striated muscles is a complex phenomenon and the provision of reliable and valid measurements requires sophisticated equipment and highly trained muscle mechanists to make the measurements and analyze and interpret the results. Consequently, to test rigorously hypotheses related to the underlying mechanisms of the reduced functionality of striated muscles in diseased and old animals, a Functionality Core is a necessity.
The specific aims of the Functionality Core are: (1) the provision of valid, state-of-the-art, functional measurements: (1a) for Project #1 of single permeabilized fibers of limb muscles and whole limb muscles of wild type, dystrophic, transgenic and mutant adult and old mice, and in mice after vector-based gene transfer; (1b) for Project #2 of single cardiac myocyte function and whole heart hemodynamics of adult and old, wild type and mutant mice, and in young and old mice and rats after vector-based gene transfer in vitro and in vivo; (1c) for Project #3 of single permeabilized fibers from flight muscles, force and power of flight muscles during tethered flight, and whole heart muscle functionality of wild type, transgenic and mutant Drosophila; (2) continuous up-dating of the design, development, and construction of innovative experimental protocols and apparatus to measure specific mechanical properties of striated muscles; (3) consultation and training of trainees and faculty to make measurements of functionality and maintain the apparatus used to measure functional properties of striated muscles of rodents and Drosophila. The significance of the Functionality Core lies in the critical role that functional properties play in the interpretation of the structure-function relationships with natural aging of the organism and following any genetic manipulation of skeletal or cardiac muscles of rodents or Drosophila. Impairments in functionality of striated muscles may occur at any age due to injury or disease or as an intractable concomitant of aging. The impairments in functionality, whether due to injury, disease, or old age, limit the activities of daily living and reduce the quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG015434-10
Application #
7404522
Study Section
Special Emphasis Panel (ZAG1)
Project Start
2007-05-01
Project End
2008-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
10
Fiscal Year
2007
Total Cost
$89,285
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Prins, Kurt W; Asp, Michelle L; Zhang, Huiliang et al. (2016) Microtubule-Mediated Misregulation of Junctophilin-2 Underlies T-Tubule Disruptions and Calcium Mishandling in mdx Mice. JACC Basic Transl Sci 1:122-130
Muir, Lindsey A; Nguyen, Quynh G; Hauschka, Stephen D et al. (2014) Engraftment potential of dermal fibroblasts following in vivo myogenic conversion in immunocompetent dystrophic skeletal muscle. Mol Ther Methods Clin Dev 1:14025
Nishimura, Mayuko; Kumsta, Caroline; Kaushik, Gaurav et al. (2014) A dual role for integrin-linked kinase and ?1-integrin in modulating cardiac aging. Aging Cell 13:431-40
Ramaswamy, Krishnan S; Palmer, Mark L; van der Meulen, Jack H et al. (2011) Lateral transmission of force is impaired in skeletal muscles of dystrophic mice and very old rats. J Physiol 589:1195-208
Claflin, Dennis R; Larkin, Lisa M; Cederna, Paul S et al. (2011) Effects of high- and low-velocity resistance training on the contractile properties of skeletal muscle fibers from young and older humans. J Appl Physiol 111:1021-30
Palmer, Mark L; Claflin, Dennis R; Faulkner, John A et al. (2011) Non-uniform distribution of strain during stretch of relaxed skeletal muscle fibers from rat soleus muscle. J Muscle Res Cell Motil 32:39-48
Gumerson, Jessica D; Kabaeva, Zhyldyz T; Davis, Carol S et al. (2010) Soleus muscle in glycosylation-deficient muscular dystrophy is protected from contraction-induced injury. Am J Physiol Cell Physiol 299:C1430-40
Kimura, En; Li, Sheng; Gregorevic, Paul et al. (2010) Dystrophin delivery to muscles of mdx mice using lentiviral vectors leads to myogenic progenitor targeting and stable gene expression. Mol Ther 18:206-13
Fink, Martin; Callol-Massot, Carles; Chu, Angela et al. (2009) A new method for detection and quantification of heartbeat parameters in Drosophila, zebrafish, and embryonic mouse hearts. Biotechniques 46:101-13
Wessells, Robert; Fitzgerald, Erin; Piazza, Nicole et al. (2009) d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila. Aging Cell 8:542-52

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