326 A. McArdle and M.J. Jackson 8 Future Directions In the light of these data we hypothesise that attenuation of the adaptive responses to contractions is a key factor leading to age-related loss of muscle mass and func- tion; ROS generated during contractions are important stimulators of adaptive responses and they originate from a source associated with the cytosol; Mitochondria release increased amounts of hydrogen peroxide and the resulting chronic oxidation blocks the normal adaptations to contractile activity through either: (1) inducing upregulation of ROS defence systems (SODs, catalase and HSPs) that suppress the cytosolic ROS signal that normally stimulates adaptive responses to contractions or (2) preventing activation of the cytosol-associated ROS generating system that are activated by contractions. 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Lynch (ed.), Sarcopenia – Age-Related Muscle Wasting and Weakness, DOI 10.1007/978-90-481-9713-2_15, © Springer Science+Business Media B.V. 2011 Abstract The aging process is characterized by the gradual decrease in muscle mass, strength and power leading to a decline in physical functioning, increased frailty and disability. This age related loss of muscle mass and function has been termed sarcopenia. The mechanisms that underlie sarcopenia are only beginning to be elucidated. However, specific modes and intensities of physical activity can both act to preserve and also increase skeletal muscle mass, strength, power in healthy and functionally limited older individuals. This effect appears to be per- vasive throughout the lifespan and there is evidence for similar responses in men and women. The focus of this chapter is on the role of exercise as a therapeutic intervention for the prevention and treatment of sarcopenia. This will be accom- plished by (1) reviewing the epidemiology on physical activity and sarcopenia (2) summarizing the molecular mechanisms associated with sarcopenia and exercise, (3) discussing the efficacy of resistance and endurance exercise or multi-modal exercise, such as the combination of aerobic and resistance exercise for the man- agement of sarcopenia. Keywords Sarcopenia • Anabolic stimuli • Molecular signaling • Exercise • Muscle mass Exercise as a Countermeasure for Sarcopenia* Donato A. Rivas and Roger A. Fielding D.A. Rivas and R.A. Fielding (*) Nutrition Exercise Physiology and Sarcopenia Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA e-mail: roger.fielding@tufts.edu * This chapter is based upon work supported by the U.S. Department of Agriculture, under agree- ment No. 58-1950-7-707. Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture. 334 D.A. Rivas and R.A. Fielding 1 Introduction The aging process is characterized by the gradual decrease in muscle mass and strength leading to a decline in physical functioning, increased frailty and disability. This age related loss of muscle mass and function has been termed sarcopenia (Rosenberg 1997). The prevalence of sarcopenia between the ages of 60–70 years is between 5% and 13% and increases to between 11% and 50% at 80 years of age (Morley 2008). The large variability in the data is the result of how sarcopenia is defined and measured. Additionally, it has been observed that a loss in muscle mass is associated with metabolic alterations such as, insulin resistance, type 2 diabetes, dyslipidaemia, and obesity that are coupled with an increase in mortality (Evans 1997). The total cost of sarcopenia to the American Health System has been reported to be approximately $18.4 billion (Morley 2008; Janssen et al. 2004). Individuals over the age of 69 years are the largest growing segment of the American population (Manton and Vaupel 1995). Therefore, therapeutic interven- tions that treat sarcopenia may have profound effects on the independence and physical functioning in the elderly. There is compelling evidence that increased physical activity in older adults is associated with decreased risk of functional limitation, disability, frailty and meta- bolic disease states (DiPietro 2001; Fielding 1995; Tanaka and Seals 2008; Kohrt and Holloszy 1995; Sugawara et al. 2002; Chin et al. 2008). Therefore, exercise may be a highly effective treatment for preventing the loss of muscle mass associ- ated with ageing (Chin et al. 2008; Fielding 1995). The focus of this chapter is on the role of exercise as a therapeutic intervention for the prevention and treatment of sarcopenia. This will be accomplished by (1) reviewing the epidemiology on physical activity and sarcopenia (2) summarizing the molecular mechanisms associated with sarcopenia and exercise, (3) discussing the efficacy of resistance and endurance exercise or multi-modal exercise, such as the combination of aerobic and resistance exercise for the management of sarcopenia. 2 Role of Lifelong Habitual Physical Activity with Changes in Muscle Mass There are several parallels between the physiological effects of aging and the adap- tation as a result of disuse and inactivity (Lynch et al. 2007; Bortz 1982; Corcoran 1991; Timiras 1994). For example, aging, disuse and inactivity all have adverse effects on the cardiovascular system such as, lowering maximal oxygen uptake and stroke volume and raising blood pressure. Body composition and metabolism are also similarly affected by aging, disuse and inactivity as seen by decreased lean body mass, increased fat mass and impaired glucose tolerance. The effects of aging, disuse and inactivity on the cardiovascular system, body composition and muscle composition are very difficult to differentiate. For example, it has been reported that 335Exercise as a Countermeasure for Sarcopenia there are changes in muscle fiber type composition as a result of aging, disuse and inactivity. However, while disuse is shown to mostly decrease the number of type 1 muscle fibers, studies on aging have revealed a reduction on the number of both Type 1 and Type 2 fibers and the specific size of type 2 fibers (Lexell et al. 1988; Larsson 1983; Larsson et al. 1978). A sedentary lifestyle during aging is associated with decreased lean body mass and increased fat mass leading to increased mortality and functional limitations (Baumgartner et al. 1999; Dziura et al. 2004; DiPietro 2001; Fielding 1995; Evans 1997). This is demonstrated in studies showing a decrease in the relative risk of cardiovascular and all cause mortality in highly active compared to moderately active and sedentary individuals (Lakatta and Levy 2003; Singh 2004; Chodzko- Zajko et al. 2009). Declines in exercise capacity throughout an individual’s life span can affect functional capacity and impinge on the ability to perform activities of daily living. Recently, Sugawara et al. (2002) observed that appendicular muscle mass relative to body mass declines with advancing age regardless of physical activity status, but is significantly higher in endurance-trained men at any age than their sedentary peers (Sugawara et al. 2002). Both aerobic and resistance exercise have been shown to increase protein synthesis, while also increasing the cross- sectional area of both myosin heavy chain (MHC) I and II, respectively (Harber et al. 2009a, b; Short et al. 2004). The decreased cardiorespiratory function and reduced muscle mass and strength observed with advancing age and a sedentary lifestyle resemble the change in these variables which occur with disuse, bedrest or reduced activity (Saltin and Rowell 1980; Bortz 1982; Chopard et al. 2009a, b). Despite the evidence demonstrating the benefits of increased physical activity on healthy aging; the Centers for Disease Control (CDC) reported that three of four older adults do not meet the minimum recommendation of a brisk walk, or similar activity, of at least 5 days each week. Studies have reported that increased physical activity during aging is associated with decreased body fat, increased relative muscle mass, reduced coronary risk profile (i.e. better insulin sensitivity and glu- cose homeostasis etc.), slower development of disability in old age, and athletes that resistance trained (RET) are ~50–60% stronger than their peers (Going et al. 1995; Sugawara et al. 2002; Hagberg et al. 1985; Seals et al. 1984a, b; Hunter et al. 2000, 2002; Klitgaard et al. 1990). The Yale Health and Aging Study, an epidemio- logical study conducted over 12 years, showed that physical activity had the ability to attenuate age related weight-loss among the elderly with chronic disease (Dziura et al. 2004). Furthermore, Baumgartner and colleagues observed that physical activity was positively correlated with muscle mass and negatively correlated with body-fat in a cross-sectional study among older men and women (Baumgartner et al. 1999). Currently it is projected that the number of elderly will double worldwide from 11% of the population to 22% by 2050 (UN 2007). Because of the rapidly expand- ing population of older adults and the accumulation of evidence showing the ben- efits of increased physical activity for healthy older adults and older adults with chronic disease, a number of guidelines and recommendations on physical activity have been introduced for this population in the last few years. For the first time, in . mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction. The FASEB Journal, 18, 355–357. 329Reactive Oxygen Species Generation and Skeletal Muscle Wasting – Implications McArdle,. release and oxidative damage in mouse hind-limb skeletal muscle during aging. Mechanisms of Ageing and Development, 127, 298–306. Marcell, T. J. (2003). Sarcopenia: causes, consequences, and preventions Applied physiology of strength and power in old age. 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