- Email: [email protected]
Exercise and Sarcopenia
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. -, no. -, 1e5, 2015 Ó Copyright 2015 by The International Society for Clinical Densitometry 1094-6950/-:1e5/$36.00 http://dx.doi.org/10.1016/j.jocd.2015.04.011
Original Article
Exercise and Sarcopenia Steven Phu,1 Derek Boersma,2 and Gustavo Duque*,1,2 1
Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW, Australia; and 2Department of Geriatric Medicine, Nepean Hospital, Penrith, NSW, Australia
Abstract Sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Without any available pharmacological intervention to sarcopenia, nonpharmacological interventions are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. Additionally, to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle through improving muscle mass, strength, and function. In this review, we looked at the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population. We conclude that, although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life. Key Words: Sarcopenia; exercise; protein supplements. prevalent finding in the frailty syndrome, for this reason we propose that the positive effect of exercise is directly associated with beneficial changes in the structure and function of sarcopenic muscle. In addition, sarcopenia in frail older persons is associated with increased risk of disability and allcause mortality, which could also be prevented by regular physical activity (1). In this review, we will focus on the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population.
Introduction Considering that the three components of sarcopenia are low muscle mass, low muscle strength, and poor physical performance, developing cost-effective interventions to improve all these components in sarcopenic patients remain a major challenge. While nutritional interventions are effective to improve muscle strength and physical performance without increasing muscle mass (1), the recently reported myostatin antibodies have shown a positive effect on muscle volume without demonstrating a major effect on physical performance (2). In contrast, exercise could be the most effective intervention for sarcopenia in older persons. It is well known that exercise has a beneficial effect on muscle mass, muscle strength, and physical performance (3). Since sarcopenia is the most
Effect of Exercise on the Biology of Sarcopenia Sarcopenia is associated with changes in skeletal muscle biology (Table 1) (3e5). These mechanisms could be summarized as metabolic, cellular, vascular, and inflammatory. Metabolic changes have been associated with the mammalian target of rapamycin (mTOR) kinase, which is a key regulator of cell growth and an important sensor of nutritional status. In the normal muscle, mTOR activation controls protein synthesis in the muscle in response to exercise and nutrition, a process that is dysfunctional in the sarcopenic muscle (3e5).
Received 04/28/15; Accepted 04/29/15. *Address correspondence to: Gustavo Duque, MD, PhD, FRACP, Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, PO Box 63, Penrith, NSW, 2751, Australia. E-mail: [email protected]
1
2
Phu, Boersma, and Duque
Table 1 Biological Features of Sarcopenia Biology of sarcopenia Decreased motor units Chronic inflammation (IL-6, TNF-a, CRP) Increased oxidative stress Decreased satellite cells (number, recruitment, and repair) Decreased muscle capillarity Fat infiltration (within and between the myofibrils) Decreased PGC1a, PPARd, and mFABP Decreased mTOR Insulin resistance Increased DNA damage/apoptosis Decreased mitochondrial compartment
Exercise
Protein supplementation
Increases motor units Down regulates inflammation Endurance exercise regulates oxidative stress Increases satellite cells recruitment and repair Endurance exercise increases muscle capillarity Decreases fat infiltration and prevents lipotoxicity Increases PGC1a, PPARd, and mFABP Increases mTOR Prevents insulin resistance
Increases motor units Down regulates inflammation
Increases satellite cells recruitment and repair and facilitates the synthesis of myofibrillar proteins
Increases PGC1a, PPARd, and mFABP Increases mTOR Protects DNA from damage
Increases mitochondrial compartment
Increases mitochondrial compartment
Note: Effect of exercise and protein supplementation. Abbr: TNF-a, tumor necrosis factor alpha; CRP, C-reactive protein; mFABP, muscle fatty acid binding protein; mTOR, mammalian target of rapamycin; PGC1a, peroxisome proliferator-activated receptor gamma, coactivator 1 alpha; PPARd, Peroxisome proliferator-activated receptor delta.
In terms of cellular mechanisms, loss of muscle fiber number and fiber atrophy, particularly type II fibers, is the principal cause of sarcopenia. In addition, myofibrillar protein is reduced due to lack of capacity of the satellite cells to respond to growth factors and cytokines, which are required to stimulate their production of these proteins thus affecting the number of active satellite cells and muscle fibers (3,4). In addition, fat infiltration of muscle (within and between the fibers) is a third cellular mechanism of sarcopenia that has been recently explored (2e4). The pathophysiology of this phenomenon is explained by changes in the differentiation pattern of the satellite cells with predominant differentiation into adipocytes. The effect of this fat infiltration includes the release of toxic adipokines and fatty acids that also affect the differentiation and function of cells in their vicinity, a process known as lipotoxicity (2). In terms of the vascular mechanisms for sarcopenia, there is a reduction in capillary density that is associated with low muscle perfusion, increasing oxidative stress, and mitochondrial dysfunction. These changes are associated with reduced levels of expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a factor involved in the formation of type I fibers that activates mitochondrial genes and muscle fatty acid binding protein, which is involved in the utilization of fatty acids for energy production in the mitochondria (3).
Finally, sarcopenia is also associated with the inflammatory changes observed in frail older persons (1). Those changes are associated with high levels of C-reactive protein, interleukin 6, and tumor necrosis factor alpha. High levels of these inflammatory markers have been associated with reduced muscle mass and strength in senescent rodents. Interestingly, as shown in Table 1, exercise has an effect on all these mechanisms (1,3e5). Mechanical loading activates mTOR; thus, induces muscle protein synthesis. Exercise also increases myofibrillar protein through the activation of satellite cells. In addition, recent evidence has demonstrated that exercise decreases fat infiltration in muscle. In terms of mitochondrial function, exercise also increases proliferatoractivated receptor gamma coactivator 1-alpha and muscle fatty acid binding protein with subsequent activation of mitochondrial genes while optimizing their energy production. Finally, exercise is a strong down regulator of inflammation as demonstrated by clinical studies reporting a reduction in C-reactive protein and interleukin 6 levels in frail older persons. In summary, the overall effect of exercise on the biological mechanisms of sarcopenia could explain the benefits observed in muscle strength, mass, and performance, which have been observed in clinical trials, thus providing a biological explanation for the beneficial response to exercise in sarcopenic older patients.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
Exercise and Sarcopenia
The Effect of Exercise on the Clinical Features of Sarcopenia Effect of Exercise on Muscle Mass and Strength Exercise training represents an effective interventional strategy to attenuate and even reverse the age-related loss of muscle mass and strength (3). As previously described, exercise improves muscle mass through the activation of the satellite cell differentiation and activity. However, this beneficial effect is not always associated with an improvement in muscle strength in clinical trials. This finding is probably due to the variability in the exercise regimes and the usually small number of participants included in these trials. Nevertheless, and independently of an effect of the exercise regimes on muscle mass, resistance exercise programs are mostly effective in increasing muscle strength in sarcopenic frail older persons. The benefit of these exercise programs correlates with the intensity and the frequency of the exercise regimes used in the trials. In terms of the biological changes observed in the sarcopenic muscle, a study by Goodpaster et al (6) compared the effects of a combination of aerobic, strength, flexibility, and balance training exercises program compared with a health educational program in 42 sedentary, community dwellers (11 men and 31women, mean age 77.1 1 yr). The subjects in the education group showed a decrease in muscle mass associated with an increase in muscle fat infiltration. This finding is important because although the effect of exercise on body fat mass is well known, its effect on muscle fat was not previously assessed in clinical trials. In summary, resistance exercise training is an effective intervention in sarcopenic older persons. Because resistance exercise training is effective in increasing muscle mass and strength, endurance exercise training seems to improve maximum aerobic capacity. However, the variability of the clinical trials in terms of population, setting, and exercise regimes suggests that more standardized clinical trials are still required.
Effect of Exercise on Functional Performance Improvements in muscle mass and strength are not always associated with better functional performance in sarcopenic older persons. Poor functional performance is a predictor of poor outcomes such as falls and disability. In addition, when associated with other risk factors (smoking, hypertension, obesity, etc.) poor function is also associated with frailty and higher mortality. The evidence for the effect of physical activity on functional performance is still limited to observational studies. After adjusting for several confounders, those studies have demonstrated that sedentariness associates with poor functional performance and early disability (7). A recent intervention trial, the Lifestyle Interventions and Independence for Elders Study (8), compared a physical exercise program with a successful aging program in more than 1600 sedentary older persons followed for 3 yr. The intervention group included walking at a moderate intensity, balance, stretching, resistance exercises, and behavioral counseling.
3 The control group (successful aging) attended health education seminars and upper extremity stretching exercises. After an average of 2.6 yr follow-up, their results showed that the Short Physical Performance Battery score was significantly improved in the intervention group as compared with the control group, thus suggesting that a combination of resistance and endurance exercise could be the right approach to prevent disability and frailty in older persons. However, further randomized controlled clinical trials testing this hypothesis are still required.
Combination of Nutrition and Exercise: an Effective Therapeutic Intervention in Sarcopenia Poor nutritional status, mainly represented by low calcium and protein intake and low levels of vitamin D, are commonly found in sarcopenic frail older persons (9). Although low calcium intake is mostly related to low bone mass, it could also be associated with osteosarcopenia (10). Considering that vitamin D signaling plays a role in myogenesis, vitamin D supplementation has been proposed as a potential treatment for sarcopenia. However, large studies employing standardized, reproducible assessments of muscle strength, and double-blinded treatment regimens with and without exercise are required to delineate the effect of vitamin D supplementation on muscle function and guide recommendations regarding vitamin D intake. In terms of the effect of protein supplementation and exercise on muscle loss, there is growing biological and clinical evidence showing that these interventions could have an additive beneficial effect (9,11,12). Nutritional intervention (including protein in the diet þ/ protein supplements) provide a major therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Considering that exercise has also a direct effect on satellite cell function and body composition, it would be expected that a combination of nutritional supplements and exercise would have an additive and more beneficial effect in sarcopenic older persons. Several clinical trials have tested the effects of protein supplementation with and without exercise on muscle mass and performance in sarcopenic frail older subjects (summarized in Refs. 3 and 9). Overall, there is evidence to support an interaction between exercise and dietary protein and protein supplements on muscle mass, especially when combined with resistance exercise training (12). However, a question that remains unsolved is the optimal timing of protein consumption in relation to exercise. Considering that the best anabolic benefit of exercise occurs within 60 min after exercise, it is during this period of time post-exercise in which the patients should consume their protein supplements, which is expected to increase the availability of the amino acids required during the anabolic process (3,9). In summary, the combination of exercise and protein supplementation is a very effective intervention to improve bone mass and treat sarcopenia, thus preventing frailty and disability. Further studies are also required to evaluate whether other
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
4
Phu, Boersma, and Duque Table 2 Essential Components of an Exercise Program for Sarcopenic Older Persons
Exercise in sarcopeniadgeneral recommendations Identify patient’s preferences (i.e., time of the day, exercise history, cultural norms, etc.). Establish short-term and long-term goals. Design an activity plan including frequency (at least 3 times/wk), intensity, and type of exercise. Progressively increase duration and intensity. Perform regular evaluations of the program and the patient’s progress. Recommend proper warm up and stretching (5 min before exercise). Assure regular supervision to avoid injuries and increase motivation. Combine with protein supplements (taken within 60 min post-exercise). dietary factors, such as vitamin D and omega-3 fatty acids, or a combination of dietary factors or nutritional supplementation, can improve the effects of exercise on bone and muscle health in this particular population.
Exercise Recommendations in Sarcopenia Due to the variability of clinical trials that have tested the effectiveness of exercise in sarcopenia, establishing a set of recommended protocols for physical activity in a regular clinical practice is somewhat challenging. Nevertheless, there are some components of exercise programs that are common to most of the trials, which have demonstrated to be effective and easy to follow in the community setting (summarized in Table 2). The first major component should be the selection of an appropriate type of exercise. As previously mentioned, resistance exercise training is more effective in increasing muscle mass and strength. In contrast, endurance exercises maintain and improve maximum aerobic power, improve muscle performance, and prevent future disability (3). Finally, balance exercises are effective in patients with postural instability, which is a common finding in sarcopenic patients. In terms of frequency, a regular exercise schedule should involve at least three sessions a week with at minimal duration of 30 min for at least 6 mo. For resistance training, the recommendation is 8e10 exercises targeting different muscle groups, with 8e12 repetitions, performed twice a week on nonconsecutive days. Most benefits are observed when programs are tailored to the individual and when the exercise program progressed on a regular basis as the participants improve their exercise capacity. Such regimes require a good level of negotiation between clinicians and their patients, should establish clear goals, should individualize the programs according to functional status and comorbidities, and should make progressive changes in duration and effort while performing regular reviews of the patient’s progress.
In conclusion, sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Given the current absence of pharmacological interventions for sarcopenia, non-pharmacological approaches are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. In addition to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle improving muscle mass, strength, and function. Although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life.
Key Points Physical activity, with or without protein supplementation, improves muscle mass and function in older adults. Exercise could have direct beneficial effects on basic mechanisms causing sarcopenia including, among others, reduction of inflammation, increased satellite cells, and reduced fat infiltration. Evidence supports an interaction of exercise and protein on muscle; protein intake should occur within 60 min of exercise. Elders are encouraged to participate in a regular exercise schedule that includes at least three sessions a week with a minimal duration of 30 min.
References 1. Cruz-Jentoft AJ, Landi F. 2014 Sarcopenia. Clin Med 14:183e186. 2. Demontiero O, Boersma D, Suriyaarachchi P, Duque G. 2014 Clinical outcomes of impaired muscle and bone interactions. Clinic Rev Bone Miner Metab 12:86e92. 3. Landi F, Marzetti E, Martone AM, et al. 2014 Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care 17:25e31. 4. Vina J, Borras C, Sanchis-Gomar F, et al. 2014 Pharmacological properties of physical exercise in the elderly. Curr Pharm Des 20:3019e3029. 5. Marzetti E, Calvani R, Bernabei R, Leeuwenburgh C. 2012 Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailtyda mini-review. Gerontology 58:99e106. 6. Goodpaster BH, Chomentowski P, Ward BK, et al. 2008 Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol 105:1498e1503.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
Exercise and Sarcopenia 7. Gianoudis J, Bailey CA, Daly RM. 2014 Associations between sedentary behaviour and body composition, muscle function and sarcopenia in community-dwelling older adults. Osteoporos Int 26:571e579. 8. Pahor M, Guralnik JM, Ambrosius WT, et al. 2014 Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311:2387e2396. 9. Dickinson JM, Volpi E, Rasmussen BB. 2013 Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle. Exerc Sport Sci Rev 41:216e223.
5 10. Huo R, Suriyaarachchi P, Gomez F, et al. 2015 Comprehensive nutritional status in sarco-osteoporotic older fallers. J Nutr Health Aging 19:474e480. 11. Tieland M, van de Rest O, Dirks ML, et al. 2012 Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 13:720e726. 12. Fiatarone MA, O’Neill EF, Ryan ND, et al. 1994 Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330: 1769e1775.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
Original Article
Exercise and Sarcopenia Steven Phu,1 Derek Boersma,2 and Gustavo Duque*,1,2 1
Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, Penrith, NSW, Australia; and 2Department of Geriatric Medicine, Nepean Hospital, Penrith, NSW, Australia
Abstract Sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Without any available pharmacological intervention to sarcopenia, nonpharmacological interventions are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. Additionally, to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle through improving muscle mass, strength, and function. In this review, we looked at the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population. We conclude that, although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life. Key Words: Sarcopenia; exercise; protein supplements. prevalent finding in the frailty syndrome, for this reason we propose that the positive effect of exercise is directly associated with beneficial changes in the structure and function of sarcopenic muscle. In addition, sarcopenia in frail older persons is associated with increased risk of disability and allcause mortality, which could also be prevented by regular physical activity (1). In this review, we will focus on the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population.
Introduction Considering that the three components of sarcopenia are low muscle mass, low muscle strength, and poor physical performance, developing cost-effective interventions to improve all these components in sarcopenic patients remain a major challenge. While nutritional interventions are effective to improve muscle strength and physical performance without increasing muscle mass (1), the recently reported myostatin antibodies have shown a positive effect on muscle volume without demonstrating a major effect on physical performance (2). In contrast, exercise could be the most effective intervention for sarcopenia in older persons. It is well known that exercise has a beneficial effect on muscle mass, muscle strength, and physical performance (3). Since sarcopenia is the most
Effect of Exercise on the Biology of Sarcopenia Sarcopenia is associated with changes in skeletal muscle biology (Table 1) (3e5). These mechanisms could be summarized as metabolic, cellular, vascular, and inflammatory. Metabolic changes have been associated with the mammalian target of rapamycin (mTOR) kinase, which is a key regulator of cell growth and an important sensor of nutritional status. In the normal muscle, mTOR activation controls protein synthesis in the muscle in response to exercise and nutrition, a process that is dysfunctional in the sarcopenic muscle (3e5).
Received 04/28/15; Accepted 04/29/15. *Address correspondence to: Gustavo Duque, MD, PhD, FRACP, Musculoskeletal Ageing Research Program, Sydney Medical School Nepean, The University of Sydney, PO Box 63, Penrith, NSW, 2751, Australia. E-mail: [email protected]
1
2
Phu, Boersma, and Duque
Table 1 Biological Features of Sarcopenia Biology of sarcopenia Decreased motor units Chronic inflammation (IL-6, TNF-a, CRP) Increased oxidative stress Decreased satellite cells (number, recruitment, and repair) Decreased muscle capillarity Fat infiltration (within and between the myofibrils) Decreased PGC1a, PPARd, and mFABP Decreased mTOR Insulin resistance Increased DNA damage/apoptosis Decreased mitochondrial compartment
Exercise
Protein supplementation
Increases motor units Down regulates inflammation Endurance exercise regulates oxidative stress Increases satellite cells recruitment and repair Endurance exercise increases muscle capillarity Decreases fat infiltration and prevents lipotoxicity Increases PGC1a, PPARd, and mFABP Increases mTOR Prevents insulin resistance
Increases motor units Down regulates inflammation
Increases satellite cells recruitment and repair and facilitates the synthesis of myofibrillar proteins
Increases PGC1a, PPARd, and mFABP Increases mTOR Protects DNA from damage
Increases mitochondrial compartment
Increases mitochondrial compartment
Note: Effect of exercise and protein supplementation. Abbr: TNF-a, tumor necrosis factor alpha; CRP, C-reactive protein; mFABP, muscle fatty acid binding protein; mTOR, mammalian target of rapamycin; PGC1a, peroxisome proliferator-activated receptor gamma, coactivator 1 alpha; PPARd, Peroxisome proliferator-activated receptor delta.
In terms of cellular mechanisms, loss of muscle fiber number and fiber atrophy, particularly type II fibers, is the principal cause of sarcopenia. In addition, myofibrillar protein is reduced due to lack of capacity of the satellite cells to respond to growth factors and cytokines, which are required to stimulate their production of these proteins thus affecting the number of active satellite cells and muscle fibers (3,4). In addition, fat infiltration of muscle (within and between the fibers) is a third cellular mechanism of sarcopenia that has been recently explored (2e4). The pathophysiology of this phenomenon is explained by changes in the differentiation pattern of the satellite cells with predominant differentiation into adipocytes. The effect of this fat infiltration includes the release of toxic adipokines and fatty acids that also affect the differentiation and function of cells in their vicinity, a process known as lipotoxicity (2). In terms of the vascular mechanisms for sarcopenia, there is a reduction in capillary density that is associated with low muscle perfusion, increasing oxidative stress, and mitochondrial dysfunction. These changes are associated with reduced levels of expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a factor involved in the formation of type I fibers that activates mitochondrial genes and muscle fatty acid binding protein, which is involved in the utilization of fatty acids for energy production in the mitochondria (3).
Finally, sarcopenia is also associated with the inflammatory changes observed in frail older persons (1). Those changes are associated with high levels of C-reactive protein, interleukin 6, and tumor necrosis factor alpha. High levels of these inflammatory markers have been associated with reduced muscle mass and strength in senescent rodents. Interestingly, as shown in Table 1, exercise has an effect on all these mechanisms (1,3e5). Mechanical loading activates mTOR; thus, induces muscle protein synthesis. Exercise also increases myofibrillar protein through the activation of satellite cells. In addition, recent evidence has demonstrated that exercise decreases fat infiltration in muscle. In terms of mitochondrial function, exercise also increases proliferatoractivated receptor gamma coactivator 1-alpha and muscle fatty acid binding protein with subsequent activation of mitochondrial genes while optimizing their energy production. Finally, exercise is a strong down regulator of inflammation as demonstrated by clinical studies reporting a reduction in C-reactive protein and interleukin 6 levels in frail older persons. In summary, the overall effect of exercise on the biological mechanisms of sarcopenia could explain the benefits observed in muscle strength, mass, and performance, which have been observed in clinical trials, thus providing a biological explanation for the beneficial response to exercise in sarcopenic older patients.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
Exercise and Sarcopenia
The Effect of Exercise on the Clinical Features of Sarcopenia Effect of Exercise on Muscle Mass and Strength Exercise training represents an effective interventional strategy to attenuate and even reverse the age-related loss of muscle mass and strength (3). As previously described, exercise improves muscle mass through the activation of the satellite cell differentiation and activity. However, this beneficial effect is not always associated with an improvement in muscle strength in clinical trials. This finding is probably due to the variability in the exercise regimes and the usually small number of participants included in these trials. Nevertheless, and independently of an effect of the exercise regimes on muscle mass, resistance exercise programs are mostly effective in increasing muscle strength in sarcopenic frail older persons. The benefit of these exercise programs correlates with the intensity and the frequency of the exercise regimes used in the trials. In terms of the biological changes observed in the sarcopenic muscle, a study by Goodpaster et al (6) compared the effects of a combination of aerobic, strength, flexibility, and balance training exercises program compared with a health educational program in 42 sedentary, community dwellers (11 men and 31women, mean age 77.1 1 yr). The subjects in the education group showed a decrease in muscle mass associated with an increase in muscle fat infiltration. This finding is important because although the effect of exercise on body fat mass is well known, its effect on muscle fat was not previously assessed in clinical trials. In summary, resistance exercise training is an effective intervention in sarcopenic older persons. Because resistance exercise training is effective in increasing muscle mass and strength, endurance exercise training seems to improve maximum aerobic capacity. However, the variability of the clinical trials in terms of population, setting, and exercise regimes suggests that more standardized clinical trials are still required.
Effect of Exercise on Functional Performance Improvements in muscle mass and strength are not always associated with better functional performance in sarcopenic older persons. Poor functional performance is a predictor of poor outcomes such as falls and disability. In addition, when associated with other risk factors (smoking, hypertension, obesity, etc.) poor function is also associated with frailty and higher mortality. The evidence for the effect of physical activity on functional performance is still limited to observational studies. After adjusting for several confounders, those studies have demonstrated that sedentariness associates with poor functional performance and early disability (7). A recent intervention trial, the Lifestyle Interventions and Independence for Elders Study (8), compared a physical exercise program with a successful aging program in more than 1600 sedentary older persons followed for 3 yr. The intervention group included walking at a moderate intensity, balance, stretching, resistance exercises, and behavioral counseling.
3 The control group (successful aging) attended health education seminars and upper extremity stretching exercises. After an average of 2.6 yr follow-up, their results showed that the Short Physical Performance Battery score was significantly improved in the intervention group as compared with the control group, thus suggesting that a combination of resistance and endurance exercise could be the right approach to prevent disability and frailty in older persons. However, further randomized controlled clinical trials testing this hypothesis are still required.
Combination of Nutrition and Exercise: an Effective Therapeutic Intervention in Sarcopenia Poor nutritional status, mainly represented by low calcium and protein intake and low levels of vitamin D, are commonly found in sarcopenic frail older persons (9). Although low calcium intake is mostly related to low bone mass, it could also be associated with osteosarcopenia (10). Considering that vitamin D signaling plays a role in myogenesis, vitamin D supplementation has been proposed as a potential treatment for sarcopenia. However, large studies employing standardized, reproducible assessments of muscle strength, and double-blinded treatment regimens with and without exercise are required to delineate the effect of vitamin D supplementation on muscle function and guide recommendations regarding vitamin D intake. In terms of the effect of protein supplementation and exercise on muscle loss, there is growing biological and clinical evidence showing that these interventions could have an additive beneficial effect (9,11,12). Nutritional intervention (including protein in the diet þ/ protein supplements) provide a major therapeutic strategy to improve the satellite cell niche and systemic factors, with the goal of improving satellite cell function in aging muscles. Considering that exercise has also a direct effect on satellite cell function and body composition, it would be expected that a combination of nutritional supplements and exercise would have an additive and more beneficial effect in sarcopenic older persons. Several clinical trials have tested the effects of protein supplementation with and without exercise on muscle mass and performance in sarcopenic frail older subjects (summarized in Refs. 3 and 9). Overall, there is evidence to support an interaction between exercise and dietary protein and protein supplements on muscle mass, especially when combined with resistance exercise training (12). However, a question that remains unsolved is the optimal timing of protein consumption in relation to exercise. Considering that the best anabolic benefit of exercise occurs within 60 min after exercise, it is during this period of time post-exercise in which the patients should consume their protein supplements, which is expected to increase the availability of the amino acids required during the anabolic process (3,9). In summary, the combination of exercise and protein supplementation is a very effective intervention to improve bone mass and treat sarcopenia, thus preventing frailty and disability. Further studies are also required to evaluate whether other
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
4
Phu, Boersma, and Duque Table 2 Essential Components of an Exercise Program for Sarcopenic Older Persons
Exercise in sarcopeniadgeneral recommendations Identify patient’s preferences (i.e., time of the day, exercise history, cultural norms, etc.). Establish short-term and long-term goals. Design an activity plan including frequency (at least 3 times/wk), intensity, and type of exercise. Progressively increase duration and intensity. Perform regular evaluations of the program and the patient’s progress. Recommend proper warm up and stretching (5 min before exercise). Assure regular supervision to avoid injuries and increase motivation. Combine with protein supplements (taken within 60 min post-exercise). dietary factors, such as vitamin D and omega-3 fatty acids, or a combination of dietary factors or nutritional supplementation, can improve the effects of exercise on bone and muscle health in this particular population.
Exercise Recommendations in Sarcopenia Due to the variability of clinical trials that have tested the effectiveness of exercise in sarcopenia, establishing a set of recommended protocols for physical activity in a regular clinical practice is somewhat challenging. Nevertheless, there are some components of exercise programs that are common to most of the trials, which have demonstrated to be effective and easy to follow in the community setting (summarized in Table 2). The first major component should be the selection of an appropriate type of exercise. As previously mentioned, resistance exercise training is more effective in increasing muscle mass and strength. In contrast, endurance exercises maintain and improve maximum aerobic power, improve muscle performance, and prevent future disability (3). Finally, balance exercises are effective in patients with postural instability, which is a common finding in sarcopenic patients. In terms of frequency, a regular exercise schedule should involve at least three sessions a week with at minimal duration of 30 min for at least 6 mo. For resistance training, the recommendation is 8e10 exercises targeting different muscle groups, with 8e12 repetitions, performed twice a week on nonconsecutive days. Most benefits are observed when programs are tailored to the individual and when the exercise program progressed on a regular basis as the participants improve their exercise capacity. Such regimes require a good level of negotiation between clinicians and their patients, should establish clear goals, should individualize the programs according to functional status and comorbidities, and should make progressive changes in duration and effort while performing regular reviews of the patient’s progress.
In conclusion, sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Given the current absence of pharmacological interventions for sarcopenia, non-pharmacological approaches are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. In addition to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle improving muscle mass, strength, and function. Although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life.
Key Points Physical activity, with or without protein supplementation, improves muscle mass and function in older adults. Exercise could have direct beneficial effects on basic mechanisms causing sarcopenia including, among others, reduction of inflammation, increased satellite cells, and reduced fat infiltration. Evidence supports an interaction of exercise and protein on muscle; protein intake should occur within 60 min of exercise. Elders are encouraged to participate in a regular exercise schedule that includes at least three sessions a week with a minimal duration of 30 min.
References 1. Cruz-Jentoft AJ, Landi F. 2014 Sarcopenia. Clin Med 14:183e186. 2. Demontiero O, Boersma D, Suriyaarachchi P, Duque G. 2014 Clinical outcomes of impaired muscle and bone interactions. Clinic Rev Bone Miner Metab 12:86e92. 3. Landi F, Marzetti E, Martone AM, et al. 2014 Exercise as a remedy for sarcopenia. Curr Opin Clin Nutr Metab Care 17:25e31. 4. Vina J, Borras C, Sanchis-Gomar F, et al. 2014 Pharmacological properties of physical exercise in the elderly. Curr Pharm Des 20:3019e3029. 5. Marzetti E, Calvani R, Bernabei R, Leeuwenburgh C. 2012 Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailtyda mini-review. Gerontology 58:99e106. 6. Goodpaster BH, Chomentowski P, Ward BK, et al. 2008 Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol 105:1498e1503.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015
Exercise and Sarcopenia 7. Gianoudis J, Bailey CA, Daly RM. 2014 Associations between sedentary behaviour and body composition, muscle function and sarcopenia in community-dwelling older adults. Osteoporos Int 26:571e579. 8. Pahor M, Guralnik JM, Ambrosius WT, et al. 2014 Effect of structured physical activity on prevention of major mobility disability in older adults: the LIFE study randomized clinical trial. JAMA 311:2387e2396. 9. Dickinson JM, Volpi E, Rasmussen BB. 2013 Exercise and nutrition to target protein synthesis impairments in aging skeletal muscle. Exerc Sport Sci Rev 41:216e223.
5 10. Huo R, Suriyaarachchi P, Gomez F, et al. 2015 Comprehensive nutritional status in sarco-osteoporotic older fallers. J Nutr Health Aging 19:474e480. 11. Tieland M, van de Rest O, Dirks ML, et al. 2012 Protein supplementation improves physical performance in frail elderly people: a randomized, double-blind, placebo-controlled trial. J Am Med Dir Assoc 13:720e726. 12. Fiatarone MA, O’Neill EF, Ryan ND, et al. 1994 Exercise training and nutritional supplementation for physical frailty in very elderly people. N Engl J Med 330: 1769e1775.
Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health
Volume
-,
2015