CHAPTER SEVEN Automated Methods for the Analysis of Skeletal Muscle Fiber Size and Metabolic Type Tatiana Y. Kostrominova * , David S. Reiner †,{ , Richard H. Haas } , Randall Ingermanson † , Patrick M. McDonough †,1 * School of Medicine-Northwest, Indiana University, Gary, Indiana, USA † Vala Sciences Inc., San Diego, California, USA { WM&G Consulting, San Diego, California, USA } Departments of Neurosciences & Pediatrics, University of California San Diego, La Jolla, California, USA 1 Corresponding author: e-mail address: pmcdonough@valasciences.com Contents 1. Introduction 276 2. Relevance of Skeletal Muscle to Human Health 278 2.1 Hormonal control of muscle mass 278 2.2 Exercise 279 2.3 Spaceflight 279 2.4 Denervation 280 2.5 Sarcopenia and cachexia 280 2.6 Muscular dystrophies 281 2.7 Diabetes 282 3. Methods for Characterizing Muscle Fiber Subtypes 283 3.1 Historical overview 283 3.2 Fiber-typing via use of myosin subtype-specific antibodies 284 4. Skeletal Muscle Metabolism 286 4.1 Characterization of muscle metabolic enzyme activity via histochemical staining 286 4.2 Skeletal muscle lipid content 288 5. Development of Automated Analysis of Skeletal Muscle 289 5.1 Early manual methods for quantifying CSA 290 5.2 Digital camera revolution and image-analysis programs 292 5.3 Automated analysis of skeletal muscle structure 294 6. Application of High-Content Analysis Methods to Analysis of Skeletal Muscle 296 6.1 CyteSeer ® 297 7. Future Directions for Automated Quantitative Analysis of Skeletal Muscle 306 7.1 Mitochondrial disease 307 7.2 Fiber-specific protein expression beyond myosin: Skeletal muscle protein expression catalogued in the Human Protein Atlas 312 International Review of Cell and Molecular Biology, Volume 306 # 2013 Elsevier Inc. ISSN 1937-6448 All rights reserved. http://dx.doi.org/10.1016/B978-0-12-407694-5.00007-9 275