Progress 06/11/04 to 04/12/06
Outputs
Progress Report 1. What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? Why does it matter? Epidemiological data suggest that over 50 percent of adults over age 75 have measurable sarcopenia - the age-associated loss in skeletal muscle, and this is associated with increased risk of disability. Skeletal muscle plays a central role in many biological functions, such as movement and metabolism, and alterations in skeletal muscle may have a marked influence on health and disease. Sarcopenia and muscle wasting (muscle loss mass caused by disease or disuse) may lead to metabolic disorders (e. g., insulin resistance) and a reduced ability to cope with illness and injury. Sarcopenia is universal in the elderly, indicating that it is age-related, while muscle wasting is a disease-related problem that may greatly exacerbate muscle loss with aging. The normal progression of sarcopenia and
muscle wasting is determined by a combination of genetic and environmental factors such as nutrition and physical activity. Sarcopenia is a contributing factor in the development of deficits in function and physical disability. Although the prevalence of chronic disability in older individuals is declining in the United States, with the continued rise in the total number of individuals over the age of 65, the number of individuals with chronic disability remains on the increase. The economic impact of sarcopenia in the United States was estimated at $18.5 billion in 2000. A careful investigation of the cellular alterations associated with sarcopenia, which include decreases in muscle fiber size, contractile, and metabolic capacity may further refine our understanding of the proximal determinants of mobility limitations and disability in the elderly. In addition, the pairing of clinical studies examining the influence of protein nutrition and physical activity on sarcopenia with basic
approaches that identify the molecular landscape and potential targets in skeletal muscle for preventive interventions (nutritional, exercise) may accelerate our ability to translate these findings to aging people. Finally, the development of novel nutritional and physical activity interventions targeted at specific pathophysiological changes and conditions in older adults with sarcopenia should continue to be examined. This project is directly responsive to the following National Program 107 - Human Nutrition program components: 4. Nutrient Requirements; 6. Prevention of Obesity and Disease: Relationship between Diet, Genetics, and Lifestyle; and 7. Health Promoting Intervention Strategies for Targeted Populations. 2. List by year the currently approved milestones (indicators of research progress) This CRIS project previously consisted of two laboratories at the time of the NP107 OSQR process. The Body Composition Laboratory, which completed the OSQR NP107 review and certification in
2004, was subsequently moved to another project in 2005. For progress and details on the Body Composition Laboratory, see CRIS Project 1950-51000-061-03A. The other laboratory, the Nutrition, Exercise Physiology and Sarcopenia Laboratory, was exempt from the original NP107 OSQR due to a hiring process for a new laboratory director. This project recently completed OSQR certification through an Ad Hoc review. For progress and details see CRIS Project 1950- 51000-066-01A. 4a List the single most significant research accomplishment during FY 2006. Contraction-mediated signaling in aging skeletal muscle. The cellular changes in response to muscle contraction ultimately cause muscle cells to increase in size but the specific way that this happens and whether these processes are affected by age are not known. Scientists examined the effect of age on the regulation of metabolic pathways that turn on muscle protein synthesis in response to muscle action or contraction. Using a well
characterized animal model for skeletal muscle aging, adult (6 months old) and aged (30 months old) Fischer 344 x Brown Norway rats were studied before and after activation (contraction) of their hindlimbs designed to mimic a weightlifting protocol in humans. The results showed that the metabolic signals associated with turning on protein synthesis in the muscle cells are increased after high frequency electrical stimulation (HFES) in adult animals, but not in aged animals. These observations suggest that the protein synthesis in response to muscle contraction is attenuated with aging and may contribute to the limited capacity of muscle growth with aging. Future studies should investigate the metabolic causes of these changes and the resultant impact on skeletal muscle protein synthesis and the influence of amino acid availability. This research is aligned to National Program 107 Human Nutrition program components: Prevention of Obesity and Disease: Relationship between Diet,
Genetics, and Lifestyle. 4b List other significant research accomplishment(s), if any. Skeletal Muscle Growth with Advancing Age The Nutrition, Exercise Physiology and Sarcopenia Laboratory developed three specific techniques using animal models to complement our clinical studies of sarcopenia. Using mice, we have established the hindlimb unloading procedure (tail suspension) to examine cellular changes in skeletal muscle due to disuse or inactivity. In addition, using the Fisher 344 X Brown Norway Rat, we have established two techniques (high frequency electrical stimulation, synergistic muscle ablation surgery) to identify both the acute and chronic effects of muscle contraction (exercise) on the control muscle cell growth in aging animals. These techniques will enable us to conduct mechanistic studies examining the influence of contractile activity and protein nutrition on the control of skeletal muscle growth with advancing age. This research is aligned to National Program 107
Human Nutrition program components: Prevention of Obesity and Disease: Relationship between Diet, Genetics, and Lifestyle. Strong Living Community-based Exercise Program The Strong Living Program is a self-sustaining network of community-based group exercise programs for older adults in New England. The two fundamental components of the program include a research-based strength training program and an educational training workshop for community leaders to disseminate the program. Participants perform weight lifting, flexibility and balance exercises using low-cost ankle weights and dumbbells. All exercises are uniquely designed with different levels of difficulty to accommodate a wide range of abilities. Exercise classes are held at convenient, local settings including community centers, councils on aging, town halls, and churches. The groups meet twice weekly for approximately one hour. Our dissemination model is based on identifying potential program leaders both allied health
professionals and peers, training them in hands-on, interactive workshops, and certifying them based on practical and written competency in exercise technique and program administration. The program began in pilot form in 1995 and has continued as the Strong Living Program since 1998. We currently have 94 community program sites, 189 certified leaders, and over 2,000 participants ranging from 40 to 95 years of age (most are over 70 years). After three months of exercising with the Strong Living Program, older adults significantly improve their strength, mobility, balance and functional status. Participants also report improved self-confidence and benefits from the opportunity to socialize. Our long-term goal is to develop the Strong Living Program into a nation-wide public health initiative to increase physical activity, reduce the risk and burden of chronic disease, and improve quality of life in older adults. This research is aligned to National Program 107 Human Nutrition program
components: Prevention of Obesity and Disease: Relationship between Diet, Genetics, and Lifestyle. 5. Describe the major accomplishments to date and their predicted or actual impact. For the past twenty years the Nutrition, Exercise Physiology, and Sarcopenia Laboratory has been at the forefront of understanding that progressive resistance training can reverse weakness and sarcopenia in frail and chronically ill elderly populations, including nursing home residents, and patients with arthritis, renal disease, heart disease, and diabetes. The laboratorys research on the adequacy of protein requirements in the elderly with or without chronic disease, has shown that a marginal protein diet (~0.6 g/kg/day) is not sufficient to maintain muscle mass, muscle function, and quality of life. Scientists have also shown that resistance exercise training, in combination with a marginal protein diet, can counteract the adverse effects of a low protein diet such as muscle loss and weakness in frail
and chronically ill elderly. Results of this research have been widely reported in the scientific and lay press. Current findings from the laboratory have provided insight into the mechanisms by which diet and exercise exert an anabolic effect in muscle tissue. Important targets we have identified as key regulators of these anabolic processes include catabolic/anabolic muscle cytokines, growth factors, and inflammatory markers. The laboratorys accomplishments are directly related to National Program 107 - Human Nutrition program components: 4. Nutrient Requirements; 6. Prevention of Obesity and Disease; Relationship between Diet, Genetics, Lifestyle; 7. Health Promoting Intervention Strategies for Targeted Populations and to Performance Measure 4.1.2 Improve Human Health by Better Understanding the Nutrient Requirements of Individuals and the Nutritional Value of Foods. This project recently completed OSQR certification through an Ad Hoc review. For progress and details see CRIS
Project 1950-51000-066-01A. 6. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end- user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? The laboratorys research findings have been presented at scientific meetings such as Experimental Biology. Papers describing these findings been published in peer-review journals. 7. List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: List your peer reviewed publications below). Roger Fielding quoted in FITNESS - A path to weight loss Yoga may not burn a lot of calories but the practice appears to stave off middle-age spread by reducing stress. Emily Singer, Los Angeles Times, August 8, 2005 The Boston Globe, Health/Science Q&A January 11, 2005 HNRCA Speaker's Bureau Dec. 6, 2005: Carmen
Sceppa, MD, Ph.D. Physical Activity and Strength Training for Harvard University retirees - Cambridge, MA ARS Magazine May 2005: Sarcopenia, nutrition and exercise, page 20 and online at http://www.ars.usda.gov/is/AR/archive/apr05/potion0405.htm
Impacts
(N/A)
Publications
- Hamada, K., Vannier, E., Sacheck, J., Witsell, A., Roubenoff, R. 2005. Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. Journal of Federation of American Societies for Experimental Biology. 19(2):264-266.
- Sigal, R.J., Kenny, G.P., Wasserman, D.H., Castaneda-Sceppa, C. 2004. Physical activity/exercise and type 2 diabetes: Technical review. Diabetes Care. 27(10):2518-2539.
- Castaneda, C., Cadena, S., Harris, S. 2005. Association of vitamin D status with changes in markers for disease risk and morbidity in older adults with type 2 diabetes [abstract]. Journal of Federation of American Societies for Experimental Biology. 19(5):A1468.
- Castaneda, F., Kinne, R.K., Castaneda-Sceppa, C. 2005. Effect of resistance training on skeletal muscle sodium-dependent glucose transport (SGLT) gene expression in older adults with type 2 diabetes [abstract]. Federation of American Societies for Experimental Biology Conference. 19(4) :A469.
- Layne, J.E., Vannier, E., Carambula, S., Castaneda-Sceppa, C. 2005. Resistance training increases serum adiponectin in older adults with type 2 diabetes [abstract]. Journal of Federation of American Societies for Experimental Biology. 19(4):A419.
- Janssen, I., Roubenoff, R. 2005. Inflammatory diseases and body composition. In: Heymsfield, Steven B., editor. Human Body Composition, 2nd edition. Champaign, Illinois: Human Kinetics. p.389-400.
- Lebrasseur, N.K., Mizer, K.C., Parkington, J.D., Sawyer, D.B., Fielding, R. A. 2005. The expression of neuregulin and erbB receptors in human skeletal muscle: effects of progressive resistance training. European Journal of Applied Physiology. 94(4):371-375.
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Progress 10/01/04 to 09/30/05
Outputs
1. What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? What does it matter? Epidemiological data suggest that over 50 percent of adults over age 75 have measurable Sarcopenia - the age-associated loss in skeletal muscle, and this is associated with increased risk of disability. Skeletal muscle plays a central role in many biological functions, such as movement and metabolism, and alterations in skeletal muscle may have a marked influence on health and disease. Sarcopenia and muscle wasting (muscle loss mass caused by disease or disuse) may lead to metabolic disorders (e. g., insulin resistance) and a reduced ability to cope with illness and injury. Sarcopenia is universal in the elderly, indicating that it is age-related, while muscle wasting is a disease-related problem that may greatly exacerbate muscle loss with aging. The normal progression of sarcopenia and muscle
wasting is determined by a combination of genetic and environmental factors such as nutrition and physical activity. Sarcopenia is a contributing factor in the development of deficits in function and physical disability. Although the prevalence of chronic disability in older individuals is declining in the United States, with the continued rise in the total number of individuals over the age of 65, the number of individuals with chronic disability remains on the increase. The economic impact of sarcopenia in the United States was estimated at $18.5 billion in 2000. A careful investigation of the cellular alterations associated with sarcopenia, which include decreases in muscle fiber size, contractile, and metabolic capacity may further refine our understanding of the proximal determinants of mobility limitations and disability in the elderly. In addition, the pairing of clinical studies examining the influence of protein nutrition and physical activity on sarcopenia with basic
approaches that identify the molecular landscape and potential targets in skeletal muscle for preventive interventions (nutritional, exercise) may accelerate our ability to translate these findings to aging people. Finally, the development of novel nutritional and physical activity interventions targeted at specific pathophysiological changes and conditions in older adults with sarcopenia should continue to be examined. This project is directly responsive to the following National Program 107 - Human Nutrition program components: 4. Nutrient Requirements; 6. Prevention of Obesity and Disease: Relationship between Diet, Genetics, and Lifestyle; and 7. Health Promoting Intervention Strategies for Targeted Populations. 2. List the milestones (indicators of progress) from your Project Plan. This CRIS project previously consisted of two laboratories at the time of the NP107 OSQR process. The Body Composition Laboratory, which completed the OSQR NP107 review and certification in 2004, was
subsequently moved to another project in 2005. For progress and details on the Body Composition Laboratory, see CRIS Project 1950-51000-061-03A. The other laboratory, the Nutrition, Exercise Physiology and Sarcopenia Laboratory, was exempt from the original NP107 OSQR due to a hiring process for a new laboratory director. This project is now pending OSQR certification through Ad Hoc review in the fall of 2005. 3a List the milestones that were scheduled to be addressed in FY 2005. For each milestone, indicate the status: fully met, substantially met, or not met. If not met, why. 1. This CRIS project previously consisted of two laboratories at the time of the NP107 OSQR process. The Body Composition Laboratory, which completed the OSQR NP107 review and certification in 2004, was subsequently moved to another project in 2005. For progress and details on the Body Composition Laboratory, see CRIS Project 1950-51000-061-03A. The other laboratory, the Nutrition, Exercise Physiology and
Sarcopenia Laboratory, was exempt from the original NP107 OSQR due to a hiring process for a new laboratory director. This project is now pending OSQR certification through Ad Hoc review in the fall of 2005. Milestone Not Met Other 3b List the milestones that you expect to address over the next 3 years (FY 2006, 2007, and 2008). What do you expect to accomplish, year by year, over the next 3 years under each milestone? This CRIS project previously consisted of two laboratories at the time of the NP107 OSQR process. The Body Composition Laboratory, which completed the OSQR NP107 review and certification in 2004, was subsequently moved to another project in 2005. For progress and details on the Body Composition Laboratory, see CRIS Project 1950-51000-061-03A. The other laboratory, the Nutrition, Exercise Physiology and Sarcopenia Laboratory, was exempt from the original NP107 OSQR due to a hiring process for a new laboratory director. This project is now pending OSQR certification
through Ad Hoc review in the fall of 2005. 4a What was the single most significant accomplishment this past year? Contraction-mediated signaling in aging skeletal muscle. The cellular changes in response to muscle contraction ultimately cause muscle cells to increase in size but the specific way that this happens and whether these processes are affected by age are not known. Scientists examined the effect of age on the regulation of metabolic pathways that turn on muscle protein synthesis in response to muscle action or contraction. Using a well characterized animal model for skeletal muscle aging, adult (6 months old) and aged (30 months old) Fischer 344 x Brown Norway rats were studied before and after activation (contraction) of their hindlimbs designed to mimic a weightlifting protocol in humans. The results showed that the metabolic signals associated with turning on protein synthesis in the muscle cells are increased after high frequency electrical stimulation (HFES) in adult
animals, but not in aged animals. These observations suggest that the protein synthesis in response to muscle contraction is attenuated with aging and may contribute to the limited capacity of muscle growth with aging. Future studies should investigate the metabolic causes of these changes and the resultant impact on skeletal muscle protein synthesis and the influence of amino acid availability. 4b List other significant accomplishments, if any. The Nutrition, Exercise Physiology and Sarcopenia Laboratory developed three specific techniques using animal models to complement our clinical studies of sarcopenia. Using mice, we have established the hindlimb unloading procedure (tail suspension) to examine cellular changes in skeletal muscle due to disuse or inactivity. In addition, using the Fisher 344 X Brown Norway Rat, we have established two techniques (high frequency electrical stimulation, synergistic muscle ablation surgery) to identify both the acute and chronic effects of muscle
contraction (exercise) on the control muscle cell growth in aging animals. These techniques will enable us to conduct mechanistic studies examining the influence of contractile activity and protein nutrition on the control of skeletal muscle growth with advancing age. The Strong Living Program is a self-sustaining network of community- based group exercise programs for older adults in New England. The two fundamental components of the program include a research-based strength training program and an educational training workshop for community leaders to disseminate the program. Participants perform weight lifting, flexibility and balance exercises using low-cost ankle weights and dumbbells. All exercises are uniquely designed with different levels of difficulty to accommodate a wide range of abilities. Exercise classes are held at convenient, local settings including community centers, councils on aging, town halls, and churches. The groups meet twice weekly for approximately one
hour. Our dissemination model is based on identifying potential program leaders both allied health professionals and peers, training them in hands-on, interactive workshops, and certifying them based on practical and written competency in exercise technique and program administration. The program began in pilot form in 1995 and has continued as the Strong Living Program since 1998. We currently have 94 community program sites, 189 certified leaders, and over 2,000 participants ranging from 40 to 95 years of age (most are over 70 years). After three months of exercising with the Strong Living Program, older adults significantly improve their strength, mobility, balance and functional status. Participants also report improved self-confidence and benefits from the opportunity to socialize. Our long-term goal is to develop the Strong Living Program into a nation-wide public health initiative to increase physical activity, reduce the risk and burden of chronic disease, and improve
quality of life in older adults. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. For the past twenty years the Nutrition, Exercise Physiology, and Sarcopenia Laboratory has been at the forefront of understanding that progressive resistance training can reverse weakness and sarcopenia in frail and chronically ill elderly populations, including nursing home residents, and patients with arthritis, renal disease, heart disease, and diabetes. The laboratorys research on the adequacy of protein requirements in the elderly with or without chronic disease, has shown that a marginal protein diet (0.6 g/kg/day) is not sufficient to maintain muscle mass, muscle function, and quality of life. Scientists have also shown that resistance exercise training, in combination with a marginal protein diet, can counteract the adverse effects of a low protein diet such as muscle loss and weakness in frail and chronically ill elderly. Results
of this research have been widely reported in the scientific and lay press. Current findings from the laboratory have provided insight into the mechanisms by which diet and exercise exert an anabolic effect in muscle tissue. Important targets we have identified as key regulators of these anabolic processes include catabolic/anabolic muscle cytokines, growth factors, and inflammatory markers. The laboratorys accomplishments are directly related to National Program 107 - Human Nutrition program components: 4. Nutrient Requirements; 6. Prevention of Obesity and Disease; Relationship between Diet, Genetics, Lifestyle; 7. Health Promoting Intervention Strategies for Targeted Populations and to Performance Measure 4.1.2 Improve Human Health by Better Understanding the Nutrient Requirements of Individuals and the Nutritional Value of Foods. In October of 2004, Dr. Roger A. Fielding was appointed as the Director of the Nutrition, Exercise Physiology, and Sarcopenia Laboratory. Dr. Fieldings
research interests include the impact of exercise and physical activity on successful human aging, skeletal muscle alterations with advancing age in disabled and non-disabled populations, and age-related alterations in the control of skeletal muscle protein turnover. His research interests and planned projects have been incorporated into the pending CRIS project plan submitted for Ad Hoc review through OSQR. 6. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end- user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? The laboratorys research findings have been presented at scientific meetings such as Experimental Biology. Papers describing these findings been published in peer-review journals. 7. List your most important publications in the popular press and presentations to organizations and articles written
about your work. (NOTE: List your peer reviewed publications below). Roger Fielding quoted in FITNESS - A path to weight loss Yoga may not burn a lot of calories but the practice appears to stave off middle-age spread by reducing stress. Emily Singer, Los Angeles Times, August 8, 2005 The Boston Globe, Health/Science Q&A January 11, 2005 HNRCA Speaker's Bureau Dec. 6, 2005: Carmen Sceppa, MD, Ph.D. Physical Activity and Strength Training for Harvard University retirees - Cambridge, MA ARS Magazine May 2005: Sarcopenia, nutrition and exercise, page 20 and online at http://www.ars.usda.gov/is/AR/archive/apr05/potion0405.htm
Impacts
(N/A)
Publications
- Layne, J.E., Vannier, E., Carambula, S., Castaneda-Sceppa, C. 2005. Resistance training increases serum adiponectin in older adults with type 2 diabetes [abstract]. Journal of Federation of American Societies for Experimental Biology. 19(4):A419.
- Janssen, I., Roubenoff, R. 2005. Inflammatory diseases and body composition. In: Heymsfield, Steven B., editor. Human Body Composition, 2nd edition. Champaign, Illinois: Human Kinetics. p.389-400.
- Lebrasseur, N.K., Mizer, K.C., Parkington, J.D., Sawyer, D.B., Fielding, R. A. 2005. The expression of neuregulin and erbB receptors in human skeletal muscle: effects of progressive resistance training. European Journal of Applied Physiology. 94(4):371-375.
- Hamada, K., Vannier, E., Sacheck, J., Witsell, A., Roubenoff, R. 2005. Senescence of human skeletal muscle impairs the local inflammatory cytokine response to acute eccentric exercise. Journal of Federation of American Societies for Experimental Biology. 19(2):264-266.
- Sigal, R.J., Kenny, G.P., Wasserman, D.H., Castaneda-Sceppa, C. 2004. Physical activity/exercise and type 2 diabetes: Technical review. Diabetes Care. 27(10):2518-2539.
- Castaneda, C., Cadena, S., Harris, S. 2005. Association of vitamin D status with changes in markers for disease risk and morbidity in older adults with type 2 diabetes [abstract]. Journal of Federation of American Societies for Experimental Biology. 19(5):A1468.
- Castaneda, F., Kinne, R.K., Castaneda-Sceppa, C. 2005. Effect of resistance training on skeletal muscle sodium-dependent glucose transport (SGLT) gene expression in older adults with type 2 diabetes [abstract]. Federation of American Societies for Experimental Biology Conference. 19(4) :A469.
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