346 D.A. Rivas and R.A. Fielding aerobic exercise bout in aging humans. This was related to increased endothelial function and an increase in the insulin-stimulated phosphorylation of mTOR, S6K1 and Akt (Fujita et al. 2007). 4.2 Resistance Exercise In contrast to aerobic exercise, resistance exercise is based on movements performed with high resistance and a small number of repetitions over a short period of time. The purpose of resistance exercise is to provide an overload stimulus that strengthens muscles. This is usually a training stimulus in the range of 60–70% of a single repetition maximum (1RM), which can lift 8–12 times to failure and is performed repeatedly with progressive intensity that induces hypertrophy (Phillips 2007). How resistance exercise is performed is no different between young and older individuals. Furthermore, studies comparing aerobic exercise-trained (AE) and resistance exercise-trained (RE) older athletes to sedentary age-matched controls have reported many physiological advantages associated with the preven- tion of age-induced diseases (Klitgaard et al. 1990). In a seminal cross-sectional study of elderly men with different training backgrounds; Klitgaard et al. (1990) reported older men (69 years), who had been strength-training approximately 12–17 years before being studied, maximal isometric torque and muscle mass, as measured by computed tomography (CT) scan of the upper arm and mid-thigh, were significantly greater than those in age-matched swimmers or runners and were similar to young sedentary controls (Klitgaard et al. 1990). The subjects examined in this study exercised an average of three times per week at approximately 70–90% of their 1RM (Klitgaard et al. 1990). Klitgaard and colleagues provide some evidence that resistance exercise is possibly a superior intervention to aerobic train- ing for the treatment of sarcopenia. The effects of resistance exercise in young healthy men and women have been well described (for early review see Kraemer and Ratamess 2004). Briefly, high intensity progressive resistance training in young adults has resulted in significant increases in dynamic strength, explosive power, and muscle mass (McCall et al. 1996; Staron et al. 1991, 1994; Anderson and Kearney 1982). The effect of resis- tance exercise on the older humans is not a potent when compared to the young. More recent studies have confirmed these findings (Kraemer et al. 2004; Glowacki et al. 2004; Campos et al. 2002; McCaulley et al. 2009; Luden et al. 2008). Aged skeletal muscle does not respond as effectively to resistance exercise, particularly at the genetic and protein-signaling level, as young skeletal muscle (Kosek et al. 2006; Petrella et al. 2005, 2006; Mayhew et al. 2009; Bamman et al. 2004; Slivka et al. 2008; Raue et al. 2009). Although there is some attenuation of the effect of resistance exercise in the old, it is established that resistance exercise is a practical and effective intervention to increase muscle strength, power and mass in the elderly even into the ninth decade of life (McCartney et al. 1995, 1996; Kostek et al. 2005; Valkeinen et al. 2005; Fiatarone et al. 1990; Ferri et al. 2003; 347Exercise as a Countermeasure for Sarcopenia Adams et al. 2001). These measures are important to the elderly population because they may reduce the relative stress imposed by activities of daily living. 4.2.1 Improving Strength A decline in dynamic, isokinetic and static muscle strength has been noted with advancing age. Muscle strength is defined as the maximum force generation capac- ity of an individual, it reaches its peak at about the third decade of life and decreases about 12–15% per decade after the age of 50 years (Larsson et al. 1979). Direct comparisons of young and older sedentary individuals have shown that older per- sons of around 70 years have approximately 60% of the force-generating ability of their younger peers of 20–30 years (Klitgaard et al. 1990). This loss of strength with aging is observed in both men and women (Lindle et al. 1997). Several studies of the elderly have suggested that muscle strength is closely associated with functional activities of daily living (Bassey et al. 1988; Jette and Branch 1981; Rantanen et al. 1994). The declines in muscle strength with age are related to impairment in function even in otherwise healthy older individuals. Investigators have documented gains in strength as a direct result of resistance training regimens throughout the lifespan (Korpelainen et al. 2006). In the young, a 2-week isokinetic resistance training program in men effectively increased isokinetic and isometric right quadricep muscle peak torque at both 60° and 240° (Akima et al. 1999). In another report in men, a 12-week high resistance strength training program resulted in an increase in isokinetic concentric (quadriceps) knee joint strength at a velocity of 30° and eccentric (hamstring) knee joint strength at velocities of 30°, 120° and 240° (Aagaard et al. 1996). The hamstring/quadriceps ratio also increased. A dynamic resistance training protocol of similar duration in men and women resulted in isometric torso rotation strength gains in men and women who exercised twice weekly (DeMichele et al. 1997). Significant gains in both upper- and lower-body strength have also been reported for studies of 6 months duration (Kirk et al. 2007). Strength gains have been reported for shorter (8–12 weeks) duration studies in older adults. Studies that have utilized similar resistance training protocols (10–12 weeks, 3 days/week, 80% of 1RM), have shown a the mean improvement in muscle strength of ~80%, post-exercise training (Balagopal et al. 2001; Brown et al. 1990; Fiatarone et al. 1994; Frontera et al. 1988; Trappe et al. 2000, 2001; Campbell et al. 1994, Harridge et al. 1999). These studies provide evidence there is a substantial increase in muscle strength in older individuals who resistance exercise. Larsson et al. (1979) first reported that a selective loss of Type 2 (fast twitch) muscle fibers is associated with a decline in strength. Frontera et al. (1988) examined the effects of a high-intensity dynamic-resistance training program in healthy older men (mean age 64 years; (Frontera et al. 1988)). Their subjects performed knee flexion and extension exercises 3 days/week at 80% of the 1RM (eight to ten repetitions) for 12 weeks. They found a 107% increase in knee extensor strength and a 226% increase in knee flexor strength. In addition, they observed an 11% increase in 348 D.A. Rivas and R.A. Fielding mid-thigh cross-sectional area as assessed by CT. Muscle biopsy analysis revealed a 33% and 27% increase in Type 1 and 2 fiber area respectively. This was the first study to demonstrate that in healthy older men dynamic high-intensity strength- training can result in marked increases in muscle strength and muscle hypertrophy (Frontera et al. 1988). Researchers using a progressive resistance training protocol in older adults observed a linear increase in dynamic strength at different time points of a 12-week study (Sousa and Sampaio 2005). In an 8-week comparison between a combined resistance/gymnasium based functional training regimen and high- and a moderate- velocity resistance training protocols, significant dynamic strength gains were reported for the combined resistance/gymnasium indicating a synergistic effect of exercise (Henwood and Taaffe 2006). However, others report a dose–response rela- tionship between high-intensity progressive resistance training and functional capacity that may explain the preponderant use of this type of resistance training (Galvao and Taaffe 2005; Seynnes et al. 2004). Gains in strength also occur with low- (Tsutsumi et al. 1997) and variable-intensity resistance training (6 months) (Hunter et al. 2001). 4.2.2 Increasing Power Although physical activity interventions that increase or maintain of muscle strength have important health implications, there is emerging evidence that muscle power generating capacity (the rate at which muscle force can be generated) may play a more important role in functional independence and fall prevention, particu- larly among older adults. Peak muscle power has only recently been examined in older individuals as a variable distinct from strength and has been shown to decline earlier and more precipitously throughout the life span (Metter et al. 1997). Lower extremity muscle power is a strong predictor of physical performance, functional mobility and risk of falling among older adults (Bean et al. 2002, 2003). Muscle power is also inversely associated with self-reported disability status in community- dwelling older adults with mobility limitations (Foldvari et al. 2000; Suzuki et al. 2001) and is a better discriminator of mobility limitations than muscle strength (Bean et al. 2003). In particular, in two separate studies of older individuals with self-reported functional limitations, peak lower extremity power has been shown to be more closely associated with gait speed than strength (Bean et al. 2002; Cuoco et al. 2004). Exercise interventions targeted at improving lower extremity muscle power in the elderly have been well-tolerated and effective (Henwood and Taaffe 2005; Earles et al. 2001; Miszko et al. 2003). Indeed, we have previously reported that an exercise regimen of high-force, high-velocity progressive resistance training resulted in a twofold increase in muscle power in older women with self-reported functional limitations, compared to traditional high-force, slow-velocity progressive resistance training (Fielding et al. 2002). Despite the observed improvements in musculoskeletal strength, few studies have examined the specific velocity of 349Exercise as a Countermeasure for Sarcopenia training and its subsequent physiological and functional effects. Fiatarone et al. (1994) have noted in their nursing home study only a 28% increase in stair climbing power in response to progressive resistance training despite over a 100% increase in strength, suggesting a disproportionate and specific rise in strength versus power with traditional resistance training (Fiatarone et al. 1994). Skelton et al. (1995) also examined changes in peak leg extensor power in response to 12 weeks of resistance training in older women (Skelton et al. 1995). They observed increases in strength of 22–27% with a non-significant increase in leg extensor power. Recently, Jozsi et al. (1999) noted a modest improvement (30%) in leg extensor power in response to 12 weeks of RE in healthy older men and women (Jozsi et al. 1999). These studies suggest that RE results in minimal improvements in peak power and that training interventions need to be designed to more closely maximize the capacity to improve peak power in older individuals. We have shown that a 16 week high velocity high force resistance training to maximize muscle power intervention is feasible, well tolerated, and can dramatically improve lower extremity muscle power in older women with self-reported disability (Fielding et al. 2002). These results have recently been confirmed in two recent randomized trials (Earles et al. 2001; Signorile et al. 2002). Recently, we have reported (Reid et al. 2008) that a short-term intervention of high-velocity high-power progressive resistance training was associated with similar improvements of lower extremity muscle power compared to traditional slow-velocity strength training in elderly adults with preexisting mobility impairments. Although both training modalities yielded similar increases of lower extremity strength in this population, high- velocity power training was associated with significant gains in specific muscle power. Future studies should directly quantify neural adaptations and physiological mechanisms to power training, and further randomized controlled trials are war- ranted to investigate the optimal training duration and volume required to elicit significant improvements of muscle power, strength and functional performance in elderly subjects who are at increased risk for subsequent disability. 4.2.3 Increasing Muscle Mass The increase in size in response to resistance training is typically given as a change in the CSA of the muscle, as measured with magnetic resonance imaging, ultra- sonography, or CT. Changes in muscle strength and size after resistance training are likely accompanied by alterations in the size of the muscle fibers that are deter- mined by immunohistochemistry. Studies that have directly compared changes in muscle mass, CSA or protein synthesis in response to resistance exercise training have noted significant increases in both males and females (Burd et al. 2009; Staron et al. 1994; Pansarasa et al. 2009; Holm et al. 2008; Hubal et al. 2005). Increases in muscle CSA by CT scanning have also been shown to be similar between men (17.5%) and women (20.4%) in response to 16 week of upper and lower extremity high intensity resistance training (Cureton et al. 1988). However, one study employing elastic bands for resistance training noted significant increases muscle 350 D.A. Rivas and R.A. Fielding fiber cross sectional areas in men but not in women in response to 8 week of training two to three sessions per week (Hostler et al. 2001). More recently, assessment of fat free mass by dual energy x-ray absorptiometry and serial CT scans to measure muscle volume have confirmed similar increases in muscle mass and volume between young men and women in response to a 6 month whole body program of progressive resistance exercise training (Roth et al. 2001a). These results suggest that resistance exercise training can increase muscle strength and mass to similar extent in both men and women. Several studies have assessed the optimal dose of resistance training required to maximize gains in muscle strength and mass in young adults. Campos et al. (2002) compared the responses to 8 weeks of progressive resistance training (Campos et al. 2002). Young healthy men were randomized to perform low repetition high intensity, intermediate repetition moderate intensity, or high repetition low intensity progressive resistance training of the lower extremities (leg press, squat, and knee extension). These authors found that there was greater muscle fiber hypertrophy and gains in muscle strength observed low repetition high intensity group and the intermediate repetition moderate intensity group compared to the high repetition low intensity group. In young women, Hisaeda et al. (1996) observed similar gains in peak torque and muscle cross sectional in response to 8 weeks of either high intensity/low repetition or high repetition/low intensity resistance training (Hisaeda et al. 1996). Studies have also examined the influence of the number of sets per- formed at each training session on changes in muscle strength and mass in response to resistance training. Ronnestad et al. (2007) demonstrated that three sets of lower body resistance exercise per session compared to one set per session was more effective in increasing muscle strength and CSA suggesting that the volume of training per session may drive the gains in muscle strength and mass (Ronnestad et al. 2007). In contrast, by varying the number of training days per week and the number of training sets performed while normalizing the total volume of work performed per week resulted in similar gains in muscle strength and CSA in young men and women (Candow and Burke 2007). The evidence from these randomized trials suggests that muscle hypertrophy from resistance training occurs in a dose- dependent manner that is primarily dependent on the intensity at which the training sessions are performed. In addition, the total volume of work performed during resistance training may also influence to magnitude of increase in muscle mass. Early studies have demonstrated the positive effects of resistance training on muscle strength and size in healthy older men and women (For background review see: Fielding 1995). A number of randomized trials have now confirmed these initial findings (Sipila and Suominen 1996; Ferri et al. 2003; Suetta et al. 2004; Tsuzuku et al. 2007), and one study has demonstrated that muscle mass can con- tinue to increase in older adults throughout 2 years of resistance training (McCartney et al. 1996). More recently, studies have examined the influence of resistance training on changes in muscle mass and the influence of age per se. Resistance exercise training interventions (RT) can increase both whole muscle and fiber CSA in older men and women. However, there is some evidence that this response may be attenuated with advancing age. Cross sectional studies of older bodybuilders 351Exercise as a Countermeasure for Sarcopenia who had been performing RE for 12–17 years were reported to have mid-thigh muscle CSA that were similar to young sedentary controls, suggesting that the ability to stimulate muscle growth is diminished with age (Klitgaard et al. 1990). In young men and women, the change in mid-thigh CSA after 4 months of high inten- sity resistance training is typically 16–23% (Cureton et al. 1988), compared to a 2.5–9.0% increase in institutionalized or frail older individuals in response to simi- lar resistance interventions (Fiatarone et al. 1990, 1994; Binder et al. 2005). Few studies have directly compared the effect of age on muscle hypertrophy utilizing a similar standardized training intervention. Welle et al. (1996) reported impaired responses of both knee and elbow flexors but not knee extensors after a whole body RE program in older compared to young men and women (Welle et al. 1996). Data from Hakkinen et al. (1998) suggest a decline in the adaptive response of the vastus lateralis from middle to old age of approximately 40% (Hakkinen et al. 1998). Lemmer et al. (2001) reported significant increase in thigh muscle CSA in both young and older adults following resistance training, however the magnitude of the increase was greater in the young (Lemmer et al. 2001). Similar results were also observed by Dionne et al. (2004) following 6 months of resistance training in young and older non-obese women (Dionne et al. 2004). In contrast, similar duration resistance training studies have examined changes in total thigh CSA and have reported similar responses in young and old (Ivey et al. 2000; Roth et al. 2001a). These findings suggest that progressive resistance training-induced increases in muscle mass can occur in older individuals but that the magnitude of this response may be attenuated, particularly in the oldest old. Conflicting evidence has been presented on the effects of gender on the anabolic response to resistance training among older adults. Several studies that have enrolled both older men and women have reported similar increases in muscle mass with resistance training (Hakkinen et al. 1998; McCartney et al. 1996; Roth et al. 2001a; Wieser and Haber 2007). Nine weeks of high intensity resistance training resulted in lower muscle volume increases in women compared to men (Ivey et al. 2000) and similar findings were reported for whole body fat free mass in response to 12 week of high intensity resistance training in moderately overweight men and women (Joseph et al. 1999). Bamman et al. (2003) have also confirmed at the cellular level a greater degree of hypertrophy of both type I and II fibers in older men compared to older women in response to 26 weeks of high intensity resistance training (Bamman et al. 2003). However, in contrast to these reports Hakkinen et al. (1998) reported a smaller increase in muscle cross sectional area in older men com- pared to older women (Hakkinen et al. 1998). 4.3 Multi-modal Exercise Therapy While the preferential mode for strength gains has been strength training (Keeler et al. 2001; Putman et al. 2004; Sarsan et al. 2006), with a bias towards eccentric exercises (Hilliard-Robertson et al. 2003), observations indicate that other modes 352 D.A. Rivas and R.A. Fielding or multi-modal training may also be highly effective in the aging population. Current guidelines stress the importance of multi-modal exercise for this cohort, including strengthening exercises, cardiovascular, flexibility, balance training and the combination of strength and endurance training (Cress et al. 2005; Baker et al. 2007; Chodzko-Zajko et al. 2009). These include but aren’t limited to: Nordic training (Mjolsnes et al. 2004), circuit weight training (Harber et al. 2004), balance training (Heitkamp et al. 2001), a combination of strength and endurance as well as endurance only protocols (Binder et al. 2002; Putman et al. 2004; LaStayo et al. 2000; Englund et al. 2005; Izquierdo et al. 2004). Putman et al. (2004) reported that concurrent strength and endurance exercise training resulted in greater fast-to-slow fiber type transitions and attenuated hypertrophy of the type I fibers compared with strength training alone (Putman et al. 2004). Futhermore, multimodal exercise training was associated with a decreased lipid profile in older women compared to strength training alone (Marques et al. 2009). In middle-aged men and women subjected to short duration physical activity interventions, strength gains were also improved with combinatory aerobics/ weight (Tsourlou et al. 2003) training protocols. The gains in strength persist throughout longer duration studies (4–6 months) in this age group (Dornemann et al. 1997; Izquierdo et al. 2005) but demonstrate that greater gains in strength begin to occur after 8 weeks of a combined resistance and endurance exercise protocol (Izquierdo et al. 2005). In older adults, investigators have implemented longer duration (4–12 months) resistance training (Galvao and Taaffe 2005; Lord et al. 1996a, b) and combinatory resistance/endurance (King et al. 2000; Izquierdo et al. 2004; Tsourlou et al. 2006; Fahlman et al. 2007; Cress et al. 1999) type regimens to successfully increase strength in an effort to counteract the late-life decline in physical functioning. While resistance training induces muscle strength gains, functional-task exercises may be more effective at coun- teracting declines in function (de Vreede et al. 2005). Investigators have sug- gested that gains in isometric and dynamic muscle strength (Tsourlou et al. 2006) as well as in isokinetic muscle strength (Galvao and Taaffe 2005) are associated with improved physical functioning. However, the gains in strength may be muscle specific and translate into improvements in only select param- eters of physical functioning as indicated in both long (Schlicht et al. 2001; Asikainen et al. 2006; Fahlman et al. 2007) and short duration exercise inter- ventions (Topp et al. 1996). Although there have been some benefits associated with multimodal exercise regiments in young and older populations. Baker et al. (2007) recently reported, in a systematic review, that limited available data suggests that multi-modal exercise has a small effect on physical, func- tional and quality of life outcomes (Baker et al. 2007). However, more investi- gation is needed on the efficacy of simultaneous prescription of multi-modal training as a treatment for improving clinically relevant outcomes, and to establish whether multi-modal exercise at adequate volumes and intensities is feasible in older populations. 353Exercise as a Countermeasure for Sarcopenia 4.4 Anabolic Signaling/Protein Synthesis Exercise of sufficient intensity and duration disrupts homeostasis initiating adaptive processes to generate new functional protein in skeletal muscle (Coffey and Hawley 2007). An essential process in the regulatory steps controlling protein synthesis is mRNA translation (Coffey and Hawley 2007). In this regard, mTOR has been implicated as an upstream mediator of protein synthesis via putative control of ribosomal biogenesis and Cap-dependent translation (Nader et al. 2005; Hannan et al. 2003; Besse and Ephrussi 2008). Moreover, the translation repressor eukaryotic translation initiation factor-4E binding protein 1 (4E-BP1) is a direct phosphorylation target of mTORC1 which de-represses 4E-BP1 inhibition of translation initiation (Besse and Ephrussi 2008). Intuitively, both endurance and resistance exercise would be expected to “switch on” translation following exer- cise and generate skeletal muscle adaptation, yet clearly identifying increased mTOR activation and subsequent 4E-BP1 phosphorylation during recovery from exercise has proved elusive. Indeed, there is limited evidence with regard to these exercise-induced phosphorylation events being associated with increased protein fractional synthetic rate (Fujita et al. 2007) likely due to the energy-consuming, catabolic state of skeletal muscle during and immediately following exercise in the fasted state. Nonetheless, as a nutrient sensor it is not surprising that amino- acid ingestion has been shown to augment exercise-induced mTOR activation and 4E-BP1 phosphorylation, and subsequent fractional synthetic rate in skeletal muscle (Koopman et al. 2007; Dreyer et al. 2008; Drummond et al. 2008; Rivas et al. 2009). It is apparent that chronic endurance and resistance training generate specificity of adaptation and subsequent divergent phenotypes (Coffey and Hawley 2007). As such, the concomitant increase in mTOR-4E-BP1 mediated translation initiation with exercise likely contributes to the specificity of training adaptation. In support of this contention, novel findings by Wilkinson and co- workers (2008) showed increased translational signalling and fractional syn- thetic rate following both endurance and resistance training (Wilkinson et al. 2008). Notably, these workers observed specificity of adaptation with chronic endurance exercise only elevating the mitochondrial protein synthetic response, while resistance training increased myofibrillar but not mitochondrial fractional synthetic rate (Wilkinson et al. 2008). Therefore, exercise-induced mTOR translation initiation following endurance and resistance exercise may enhance skeletal muscle metabolism via alternate adaptation that promotes muscle qual- ity (mitochondria) and quantity (cross-sectional area), respectively. Regardless, the apparent capacity of mTOR to promote global protein synthesis through translational processes in response to exercise is undoubtedly beneficial for the metabolic status of skeletal muscle. Several reports have identified skeletal muscle cell signaling and protein syn- thesis inconsistencies between young and older subjects after an acute bout of resistance and aerobic exercise (Kim et al. 2005a, b; Raue et al. 2006; Fujita 354 D.A. Rivas and R.A. Fielding et al. 2007; Harber et al. 2009). For example, we have previously shown a decreased phosphorylation of mTOR and S6K1 in response to muscle contrac- tion by in situ HFES in aged animals (Parkington et al. 2004; Funai et al. 2006). Rasmussen and colleagues have confirmed our findings in humans and have further reported that muscle protein synthesis was unchanged in older humans, after a single bout of resistance exercise (Dreyer et al. 2006b) and the ingestion of AA (Drummond et al. 2008), compared to young humans. Kumar et al. (2009) revealed that an acute bout of resistance exercise at different intensities stimulate myofibrillar protein synthesis and anabolic signalling in a dose-dependent man- ner in both young and old men during a fasting state (Kumar et al. 2009). The stimulatory effect of exercise peaked at 1–2 h post-exercise and was suppressed, but not delayed, in older men. Although the extent of S6K1 phosphorylation predicted the stimulation of myofibrillar protein synthesis in young men, older men did not appear to match the changes in anabolic signalling and myofibrillar protein synthesis, possibly explaining the deficiency in the muscle protein ana- bolic response. Prolonged resistance or aerobic type exercise training represent an effective therapeutic strategy to augment skeletal muscle mass and improve functional performance in the elderly. Improvements associated with chronic exercise train- ing are said to be a result of adaptation of skeletal muscle to the additive effect of an acute exercise bout over a period of time. Exercise training, in addition to the signaling events that occur with an acute bout of exercise, also leads to the increased expression of key proteins involved in the adaptation of the muscle. The compensatory overload model of synergist ablation is an attractive model because it quickly provides a large and fast hypertrophic response. This is a commonly used model to study the effects of resistance exercise training on skeletal muscle adaptations which overloads the plantaris muscle through the removal of the synergist muscles. This mechanical overload of the plantaris muscle results in significant inductions of muscle growth of ~30% after 7 days and ~100% after 35 days in young animals (Spangenburg and Booth 2006; Spangenburg et al. 2008). In an original study that demonstrated a role for mTOR phosphorylation in muscle hypertrophy; Reynolds et al. (2002) reported a ~100% increase in the phosphorylation of mTOR on Ser2448 after 14 days of muscle overload in young animals (Reynolds et al. 2002). Recently, it has been shown that anabolic signaling and muscle hypertrophy are impaired in aged skeletal muscle in response to functional overload (Thomson and Gordon 2006; Hwee and Bodine 2009; Blough and Linderman 2000; Degens and Alway 2003). Thomson and Gordon (2006) observed decreased translational signaling and muscle hypertrophy in aged skeletal muscle in response to 7 days of muscle overload (Thomson and Gordon 2006). Interestingly, the authors correlated the inhibition of translational signaling to the activation of AMPK in the aged muscle. We have recently reported, after 28 days of chronic overload, although there was an attenuation of hypertrophy in aged animals (30 months) this was not reflected in the phosphorylation of mTOR signaling components compared to adult animals (6 months) (Chale-Rush et al. in press). 355Exercise as a Countermeasure for Sarcopenia 5 Conclusion Specific modes and intensities of physical activity can both act to preserve and also increase skeletal muscle mass, strength, power, protein synthesis and anabolic sig- nalling. This effect appears to be pervasive throughout the lifespan and there is evidence for similar responses in men and women. In general, studies supported the concept that moderate to high intensity progressive resistance (strength) training exercise was most effective in improving muscle mass, strength, and power. There is extensive evidence that specific modes of physical activity can effectively increase fat free/lean body mass, strength, and power. In particular, there is exten- sive experimental evidence that performance of regular (two to four times per week) high intensity (60–80% of the one repetition maximum) progressive resis- tance (strength) training exercise can result in significant increases in muscle size, strength, and protein synthesis. Progressive resistance (strength) training has con- sistently been shown to results in improvements in skeletal muscle mass and muscle quality. However, resistance training-induced increases in muscle mass can occur in older individuals but the magnitude of this response may be attenuated, particu- larly in the oldest of the old. The directionality has been established and the observed physiological responses are improvements in muscle size, strength and power. Endurance/aerobic and other more non-traditional forms of physical activity have not been shown to consistently increase muscle mass or quality but may be associated with the prevention of loss. Acknowledgements This chapter is based upon work supported by the U.S. Department of Agriculture, under agreement No. 58-1950-7-707. Any opinions, findings, conclusion, or recom- mendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture. The authors would like to thank Dr. Sarah J. Lessard of the Joslin Diabetes Center / Harvard Medical School for the careful review and insightful comments of the manuscript. References Aagaard, P., Simonsen, E. B., Trolle, M., Bangsbo, J., Klausen, K. (1996). Specificity of training velocity and training load on gains in isokinetic knee joint strength. Acta Physiologica Scandinavica, 156, 123–9. Adams, G. R. (2002). Invited review: Autocrine/paracrine IGF-I and skeletal muscle adaptation. Journal of Applied Physiology, 93, 1159–1167. Adams, G. R. (2006). Satellite cell proliferation and skeletal muscle hypertrophy. Applied Physiology, Nutrition, and Metabolism, 31, 782–90. Adams, K. J., Swank, A. M., Berning, J. M., Sevene-Adams, P. G., Barnard, K. L., Shimp- Bowerman, J. (2001). Progressive strength training in sedentary, older African American women. Medicine and Science in Sports and Exercise, 33, 1567–1576. Akima, H., Takahashi, H., Kuno, S. Y., Masuda, K., Masuda, T., Shimojo, H., Anno, I., Itai, Y., Katsuta, S. (1999). Early phase adaptations of muscle use and strength to isokinetic training. Medicine and Science in Sports and Exercise, 31, 588–94. . overload (Thomson and Gordon 2006; Hwee and Bodine 2009; Blough and Linderman 2000; Degens and Alway 2003). Thomson and Gordon (2006) observed decreased translational signaling and muscle hypertrophy. dual energy x-ray absorptiometry and serial CT scans to measure muscle volume have confirmed similar increases in muscle mass and volume between young men and women in response to a 6 month. increase muscle strength and mass to similar extent in both men and women. Several studies have assessed the optimal dose of resistance training required to maximize gains in muscle strength and