Mean Motor Unit Forces: • FF motor units get smaller in old age and decrease in number • S motor units get bigger with no change in number • Decreased rate of force generation and POWER!! 225 200 Adult 175 Old 150 125 Maximum Isometric Force (mN) 100 75 50 25 0 FF FI FR S Kadhiresan et al., (1996) J Physiol 493:543-552. Motor Unit Classification

But first, we should explain that the current authors (Art Vander, James Sherman and Dorothy Luciano) are still very much alive, and well. They are simply ready to retire from authoring the text-- which presents us with an opportunity to bring in a fantastic new team to continue the success of the text! The original author team will still be involved in future editions and will continue to serve as "consultants" on their book. Microstructure Modified from Squire, Muscle: Design, Diversity, and Disease Benjamin/Cummings, 1986 Originally from Lazarides (1980) Nature 283:249-256.

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Shortening velocity dependent on ATPase activity Different myosin heavy chains (MHCs) have different ATPase activities. There are at least 7 separate skeletal muscle MHC genes…arranged in series on chromosome 17. Two cardiac MHC genes located in tandem on chromosome 14. The slow b cardiac MHC is the predominant gene expressed in slow fibers of mammals. Goldspink (1999) J Anat 194:323-334. Number of motor units declines during aging - extensor digitorum brevis muscle of human beings AGE-ASSOCIATED ATROPHY DUE TO BOTH… Individual fiber atrophy (which may be at least partially preventable and reversible through exercise). Loss of fibers (which as yet appears irreversible). Campbell et al., (1973) J Neurol Neurosurg Psych 36:74-182. Calcineurin is a Ca2+-regulated • serine/threonine phosphatase. • Caclineurin dephosphorylates nuclear factor of activated T cells (NFAT) transcription factors. • Dephosphorylated NFATs • translocate to the nucleus where • combinatorially with other factors they activate transcription. • A second target of calcineurin is the transcriptional co-activator, peroxisome-proliferator-activated receptor-g co-activator-1 (PGC-1a). • Activation of calcineurin in skeletal myocytes selectively up-regulates slow-fiber-specific gene promoters and the effect enhanced with PGC-1a expression • PGC-1a activates mitochondrial biogenesis. A calcineurin dependent transcriptional pathway appears to control skeletal muscle fiber type. Lin et al. (2002) Nature 418:797-801 Performance Declines with Aging --despite maintenance of physical activity 100 80 60 Performance (% of peak) 40 Shotput/Discus Marathon 20 Basketball (rebounds/game) 0 20 30 40 50 60 10 Age (years) D.H. Moore (1975) Nature 253:264-265. NBA Register, 1992-1993 Edition Degeneration-regeneration not necessary to provide muscles protection from contraction-induced injury non-trained trained passive trained isometric *different from non- -trained (p<0.05) * * Force deficit (% control) Injured fibers (% total) * Koh & Brooks (2001) Am J Physiol 281:R155-R161. Force deficit Injured fibers • Despite the increase in susceptibility to injury with aging, • and the decreased ability to recover, muscles in old • animals can be conditioned for protection from injury. • Maintenance of conditioned fibers, particularly in muscles • of elderly people, may prevent inadvertent damage during • contractions.

Only lengthening contractions result in damaged fibers * control 20 passive isometric lengthening * different from zero (p<0.05) 15 Injured fibers (% total) 10 5 0 Other Measures of Contraction-Induced Injury • immediate mechanical disruption observed by EM. • enzyme release from degenerating muscle fibers • in human beings, subjective reports of muscle soreness • in the absence of fatigue, a decrease in the development of force Koh & Brooks (2001) Am J Physiol 281:R155-R161. The Online Learning Center is designed to enhance your learning. Book-specific content such as quizzing, case studies, objectives, and web links can all be accessed by choosing from the list to the left. These materials are designed to help you succeed in your course. Eric Widmaier (Boston University), Hershel Raff (Medical College of Wisconsin), and Kevin Strang (University of Wisconsin) have taken on the challenge of maintaining the strengths and reputation of Vander's Human Physiology: The Mechanisms of Body Function. Moving beyond the listing of mere facts, it stresses the causal chains of events that constitute the mechanisms of body function. The fundamental purpose of this textbook is to present the principles and facts of human physiology in a format that is Vander's Human Physiology, thirteenth edition, carries on the tradition of clarity and accuracy, while refining and updating the content to meet the needs of today's instructors and students. The thirteenth edition features a streamlined, clinically oriented focus to the study of human body systems. It has also responded to reviewer requests for more clinical applications. Physiology Inquiries are maintained throughout the chapters. These critical-thinking questions associated with figures are just one more opportunity to add to the student's learning experience.Homeostasis: A Framework for Human Physiology Chemical Composition of the Body Cellular structure, proteins, and Metabolism Movement of Molecules Across Cell Membranes Control of Cells by Chemical Messengers Neuronal Signaling and the Structure of the Nervous System Sensory Physiology Consciousness, the Brain, and Behavior Muscle Control of Body Movement The Endocrine System Cardiovascular Physiology Respiratory Physiology The Kidneys and Regulation of Water and Inorganic Ions The Digestion and Absorption of Food Regulation of Organic Metabolism and Energy Balance Reproduction Defense Mechanisms of the Body Medical Physiology: Integration Using Clinical Cases. Ghost” fiber 3 days after initial injury Faulkner, Brooks and Zerba (1995) J Gerontol 50:B124-B129. Chemomechanical coupling – conversion of chemical energy (ATP about 7 kcal/mole) into force/movement. • ATP is unstable thermodynamically • Two most energetically favorable steps: • 1. ATP binding to myosin • 2. Phosphate release from myosin • Rate of cycling determined by M·ATPase activity and external load Adapted from Goldman & Brenner (1987) Ann Rev Physiol 49:629-636. Structural hierarchy of skeletal muscle Muscle A little less than half of the body’s mass is composed of skeletal muscle, with most muscles linked to bones by tendons through which the forces and movements developed during contractions are transmitted to the skeleton. Muscle fibers Muscle fiber Myofibril Sarcomere Modified from McMahon, Muscles, Reflexes and Locomotion Princeton University Press, 1984. weeks post * p < 0.05 * * A single prior exposure to a protocol of lengthening contractions reduced the force deficit and damaged fibers 60% non-trained 50 40 30 20 10 0 Force Deficit (% control) Injured Fibers (% total) Koh & Brooks (2001) Am J Physiol 281:R155-R161.

Disuse causes atrophy -- USE IT OR LOSE IT! Individual fiber atrophy (loss of myofibrils) with no loss in fibers. Effect more pronounced in Type II fibers. “Completely reversible” (in young healthy individuals). ATPase activity: Type I fibers light Type II fibers dark Control Prolonged bed rest Images courtesy of John Faulkner Continuum of Physical Activity strength trained endurance trained Load controls inactivity Frequency of recruitment Muscle is plastic! Muscle “adapts” to meet the habitual level of demand placed on it, i.e. level of physical activity. Level of physical activity determined by the frequency of recruit- ment and the load. Increase muscle use – endurance training – strength training (cannot be optimally trained for both strength and endurance) Decrease muscle use – prolonged bed rest –limb casting –denervation –space flight. Adapted from Faulkner, Green and White In: Physical Activity, Fitness, and Health,Ed. Bouchard, Shephard and Stephens Human Kinetics Publishers, 1994Increased use: strength training Early gains in strength appear to be predominantly due to neural factors…optimizing recruitment patterns. Long term gains almost solely the result of hypertrophy i.e. increased size.