NUTRITION, EXERCISE AND SARCOPENIA IN THE ELDERLY

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
702	6010	1010	100%

Progress 01/11/00 to 06/10/04

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? This CRIS consists of the Nutrition, Exercise Physiology, and Sarcopenia and the Body Composition laboratories. The Nutrition, Exercise Physiology, and Sarcopenia Laboratory, studies the interaction between nutrition and exercise in aging, especially as it relates to sarcopenia (the loss of muscle with age) and muscle wasting (the loss of muscle associated with chronic disease in aging). This problem is addressed from several research perspectives, using both human and animal models of muscle loss. The Body Composition Laboratory works to increase the understanding of mechanisms leading to the age-related loss of muscle mass and to develop appropriate interventions that will slow down or reverse this decline. The problem of changes in water homeostasis is also addressed using field body composition methods in nursing home residents. Current studies in the laboratory examine: a) The adequacy of the Dietary Reference Intakes (DRI) for protein in sedentary and exercising elderly men; b) Longitudinal assessment of muscle strength and body composition to determine qualitative and quantitative changes associated with the decline in muscle mass and function with aging; c) Resistance training as a non-pharmacological intervention to improve nutritional status, muscle mass, and functional capacity in older adults suffering from chronic diseases such as renal failure and diabetes; d) Effect of the timing of feeding an essential amino acid supplement and resistance exercise on the maintenance of muscle mass using bed rest as a model of disuse muscle atrophy; e) Muscle cytokine gene expression in an animal and human models of inflammatory cachexia and wasting; f) The effectiveness of community-based group exercise (The Strong Living Program) including resistance training, flexibility, stretching and balance exercises in improving functional capacity in community-dwelling older adults; g) Validation of field methods for measuring dehydration and extracellular water using deuterium and bromide isotope dilution in nursing homes; h) The relationship between nutritional status, frailty, cognitive function and hydration status in elderly residing in nursing homes. Epidemiological data suggest that over 50% of adults over age 75 have measurable sarcopenia, 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 (normal loss of muscle mass that is a universal phenomenon of aging) and muscle wasting (the loss of muscle 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. In fact, muscle homeostasis is dependent upon several anabolic and catabolic signals, including neurological, metabolic, hormonal, nutritional factors, and exercise (resistance training). Therefore, the aim of this research program is to implement a multifaceted approach to investigate the aetiology of sarcopenia and muscle wasting and to implement intervention strategies to ameliorate and/or reverse the age-related and/or disease-related loss of muscle mass with aging. It is not clear how diet composition and intake can best be altered to reduce, treat, or prevent sarcopenia. In addition, exercise, which is clearly able to treat sarcopenia and frailty of aging, also alters needs for some, but by no means all, nutrients. Furthermore, which nutrients could be used to improve physical performance in the elderly remains poorly defined. Because protein intake falls with age, it is possible that borderline protein deficiency is part of the cause of sarcopenia. Recent evidence suggests that aging is associated with a defect in the ability to synthesize muscle in response to a mixed protein-carbohydrate meal, suggesting that insulin resistance may be important to the development of sarcopenia. The results from this research program will lead to an improved understanding of the causes, consequences, prevention, and treatment of sarcopenia and muscle wasting. At an individual level, a reduction in sarcopenia and muscle wasting would lead to improved functional performance and quality of life in older persons. Given the strong effect of muscle mass on physical disability and the associated medical costs in older persons, a reduction in the prevalence of sarcopenia and muscle wasting at the population level would lead to a reduction in health care expenditures. Research conducted within this CRIS is related to the following National Program 107 - Human Nutrition components: 1. Nutrient requirements; 2. Diet, genetics, lifestyle and the risk of prevention of obesity and disease; and 5. Health promoting intervention strategies for targeted populations. 2. List the milestones (indicators of progress) from your Project Plan. To elucidate the relative contribution of nutritional, neurologic, muscular, hormonal, and immunologic factors to the development of sarcopenia in aging and age-related degenerative disorders. To determine the interactions between exercise and dietary protein, energy, and antioxidant intake in optimizing interventions against sarcopenia and frailty in the elderly. To develop novel methods to assess body composition, muscle function and muscle quality. 3. Milestones: A. Completed study to test whether aging impairs cytokine gene expression at rest and in response to acute exercise. Completed a 16 week study of resistance exercise training to test improvement in glycemic and metabolic control in Hispanic diabetics. Launched a collaborative project with three ARS NP107 Human Nutrition research centers to develop and validate a reference method for high precision body composition analysis. This collaborative project will continue through replacement projects at each location currently pending OSQR certification. B. The Nutrition, Exercise Physiology and Sarcopenia laboratory was exempt from the OSQR process but expects to develop a plan for ad hoc review in the coming year. Research plans include studies to further investigate chronic oxidative stress in diabetics and risk of cardiovascular disease and studies to address the possible impact of physical activity on prevention or development of age-related physical disability in older Americans. Replacement project was certified on March 25, 2004 by OSQR. 4. What were the most significant accomplishments this past year? A. Most Significant Accomplishment during FY2004: Much of our knowledge about the regulation of muscle protein degradation and synthesis comes from studies of acute exercise, which generally causes muscle injury and initiates inflammatory reactions. These studies have been useful to identify mechanisms through which immune cells and inflammatory mediators influence muscle degradation and repair. We tested the hypothesis that aging impairs cytokine gene expression at rest and in response to a bout of acute exercise by focusing on specific pro- and anti-inflammatory cytokines thought to regulate muscle mass (TNF-a, IL-1b, TGF-b1, IL-6, and IGF-I). Indeed, our findings show that human skeletal muscle senescence disrupts the coordinated expression of inflammatory (catabolic) and anti-inflammatory (anabolic) cytokines that otherwise follow an acute bout of eccentric exercise. These findings suggest that aging impairs the adaptive response of human skeletal muscle to eccentric exercise (a model of exercise-induced muscle injury) by differential modulation of inflammatory and anti-inflammatory cytokine gene expression. This information is relevant in our understanding of targeted interventions to prevent/reverse muscle protein degradation and enhance muscle protein synthesis in the setting of disease, injury or disuse in older adults. B. Other Significant Accomplishments: In collaboration with the HNRCA Comparative Biology Unit, Body Composition Laboratory scientists launched a collaborative project involving scientists from three ARS research Centers (Boston, Beltsville and Grand Forks). This project's objective is to utilize facilities and expertise from the three centers to develop and validate a reference method for high precision body composition analysis to replace existing technology, which focuses on bone density measurements. C. Significant activities that support special target populations. Given the high prevalence of diabetes in the elderly and particularly among minorities like Hispanic elders, searching for effective ways to improve metabolic control are crucial to maintain health and reduce the burden of this widely spread disease. We observed that 16 weeks of resistance exercise training improved glycemic and metabolic control, resulted in skeletal muscle hypertrophy, and improved functional capacity. Paralleling these findings, resistance training lead to increased antioxidant capacity and therefore, protection against oxidative stress in this population. The improvement in antioxidant capacity was associated with a) improved glycemic control (less plasma glucose available for free radical formation), and b) increased serum uric acid concentrations (a hydrophilic antioxidant responsible for 2/3 of free radical scavenging). These findings underline the importance of developing interventions intended to target modifiable risk factors such as dietary intake and physical activity in order to reduce the burden of diabetes disease. Controlling the exposure to chronic oxidative stress in diabetes may reduce the risk of cardiovascular complications observed in this high-risk patient population, and needs to be investigated further. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. The Nutrition, Exercise Physiology, and Sarcopenia Laboratory is noted for its work focusing on nutrition and exercise interventions intended to maintain and/or preserve muscle mass and muscle function. These accomplishments are linked to National Program 107 Human Nutrition. Our 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. Additionally, we have 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 populations. Our laboratory findings have been widely reported in the scientific and lay press. Current findings from our laboratory provide insight on 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. Action Plan components 1. Nutrient Requirements and 2. Diet, Genetics, Lifestyle, and the Prevention of Obesity and Disease. 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 use of progressive resistance training to promote optimal muscle hypertrophy, muscle function and improved quality of life has been reported to the scientific community at a number of professional meetings and published in peer-reviewed scientific journals. 7. List your most important publications in the popular press and presentations to organizations and articles written about your work. Drs. Sceppa and Kehayias have communicated the use of progressive resistance training to promote optimal muscle hypertrophy, muscle function and improved quality of life to the lay public. They have also been interviewed my many media outlets, including national or local TV, radio, and print outlets including: a) ReutersHealth.com 2004-04-6 (http://www.reutershealth.com/) Resistance training and renal disease (malnutrition and inflammation); b) Tufts Nutrition Magazine, Vol 5, No.1, Fall 2003, pages 8-10. Exercising Among Friends - a Strong Living Program Story http://nutrition. tufts.edu/magazine/2003fall/strongliving.html; c) Perfiles, Latino Magazine, Ano I, Vol.6, July 1, 2003. Diabetes Mellitus in Hispanic Americans.

Impacts
(N/A)

Publications

Walsmith, J., Vannier, E., Yarasheski, K., Witsell, A., Parker, R., Lemmer, J., Roubenoff, R. 2003. Patients with rheumatoid arthritis[RA] have low protein synthesis rates and elevated Tumor Necrosis Factor-alpha(TNF-alpha) and Transforming Growth Factor-beta (TGF-beta) transcript levels in skeletal muscle [abstract]. Arthristis and Rheumatism. 48(9 Suppl):S104.
Sacheck, J.M., Blumberg, J., Milbury, P.E., Cannon, J.G., Roubenoff, R.R. 2003. Vitamin E reduces muscle damage and biomarkers of oxidative stress after exercise. Journal of Federation of American Societies for Experimental Biology. 16(5):A1137.
CASTANEDA-SCEPPA, C., MAZARIEGOS, M., ZOICO, E., BERMUDEZ, O.I., PARKER, R. C., ROUBENOFF, R., SOLOMONS, N.W. INTERLEUKIN-6, SARCOPENIA AND DISABILITY IN GUATEMALAN OLDER ADULTS. JOURNAL OF FEDERATION OF AMERICAN SOCIETIES FOR EXPERIMENTAL BIOLOGY. 2004;18(4 PT I):A125.
KEHAYIAS, J.J., ROSS, E., VALTUENA, S., SHEAHAN, C.A., MURPHY-GISMONDI, P., LAUGHERY, J., MAXWELL, B., O'NEILL, M., HARRIS, G.S., MCKEE, D. BODY COMPOSITION, DEHYDRATION AND FRAILTY ASSESSMENT IN NURSING HOMES. JOURNAL OF NUTRITION HEALTH AND AGING. 2003;7:200.
CASTANDEA-SCEPPA, C. DIABETES CONTROL WITH PHYSICAL ACTIVITY AND EXERCISE. NUTRITION IN CLINICAL CARE. 2003;6:89-96.
Frontera, W.R., Hughes, V., Krivickas, L.S., Kim, S., Foldvari, M., Roubenoff, R. 2003. Strength training in older women: early and late change in whole muscle and single cells. Muscle & Nerve. 27:601-8.
Janssen, I., Baumgartner, R.N., Ross, R., Rosenberg, I.H., Roubenoff, R. 2004. Skeletal muscle cutpoints associated with elevated disability risk in older men and women. American Journal of Epidemiology. 159:413-421.
Kehayias, J.J. 2004. Use of d-t produced fast neutrons for in vivo body composition analysis: a reference method for nutritional assessment in the elderly. Analytical and Bioanalytical Chemistry 2004;379:188-191.
Nelson, M.E., Layne, J., Bernstein, M.J., Nuernberger, A., Castaneda, C., Kaliton, D., Hausdorff, J., Judge, J.O., Buchner, D., Roubenoff, R., Fiatarone Singh, M. 2004. The effects of multi-dimensional home-based exercise on functional performance in the elderly. Journal of Gerontology. 59(2):154-60.
Prelack, K., Dwyer, J., Sheridan, R., Yu, Y.M., Lydon, M., Petras, L., Stamatelatos, I.E., Kehayias, J.J. 2003. Sodium bromide by instrumental neutron activation analysis quantifies change in extracellular water space with wound closure in severely burned children. Journal Of General Surgery 2003;133:396-403.
Roubenoff, R. 2003. Sacropenia: effects on body composition and function. Journal of Gerontology. 58(11):1012-17.
Walsmith, J., Abad, L., Kehayias, J., Roubenoff, R. 2004. Tumor necrosis factor-alpha productions is associated with less body cell mass in women with rheumatoid arthritis. Journal of Rheumatology. 31(1):23-9.
ARABELOVIC, S., FATHALLA, B., WITSELL, A., VANNIER, E., PARKER, R., SMITH, D.E., ROUBENOFF, R. SELECTIVE CYTOKINE TRANSCRIPT LEVELS IN SKELETAL MUSCLE FROM OLD RATS WITH ADJUVANT ARTHRITIS. EXPERIMENTAL BIOLOGY. 2004; 18(4 PT I):A135.
Castaneda-Sceppa, C. 2004. Resistance training and diabetes [abstract]. Medicine and Science in Sports and Exercise. 36(5 Suppl):S93.
Castaneda-Sceppa, C., Johnson, E.J., Yeum, J. 2004. Antioxidant capacity in hispanic older adults with type 2 diabetes engaged in resistance training [abstract]. Medicine and Science in Sports and Exercise. 36(5 Suppl):S189.

Progress 10/01/02 to 09/30/03

Outputs
1. What major problem or issue is being resolved and how are you resolving it? This CRIS consists of the Nutrition, Exercise Physiology, and Sarcopenia and the Body Composition laboratories. The Nutrition, Exercise Physiology, and Sarcopenia Laboratory studies the interaction between nutrition and exercise in aging, especially as it relates to sarcopenia (the loss of muscle with age) and muscle wasting (the loss of muscle associated with chronic disease in aging). This problem is addressed from several research perspectives, using both human and animal models of muscle loss. The Body Composition Laboratory works to increase the understanding of mechanisms leading to the age-related loss of muscle mass and to develop appropriate interventions that will slow down or reverse this decline. The problem of changes in water homeostasis is also addressed using field body composition methods in nursing home residents. Current studies in the laboratory examine: a) The adequacy of the RDA for protein in sedentary and exercising elderly men; b) Longitudinal assessment of the changes in muscle strength and body composition, to determine qualitative and quantitative changes that may explain the decline in muscle function with aging; c) Resistance training as a non-pharmacological intervention to improve metabolic control and muscle mass in older adults with poorly controlled diabetes; d) The effectiveness of community based group exercise (The Strong Living Program) including resistance training (weight lifting), flexibility, stretching and balance exercises in improving functional capacity in community-dwelling older adults; e) Muscle cytokine gene expression in an animal model of inflammatory cachexia; f) Validation of field methods for measuring dehydration and extracellular water using deuterium and bromide isotope dilution in nursing homes; g) The relationship between nutritional status, frailty, cognitive function and hydration status in elderly residing in nursing homes. 2. How serious is the problem? Why does it matter? Epidemiological data suggest that over 50% of adults over age 75 have measurable sarcopenia, 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 (normal loss of muscle mass that is a universal phenomenon of aging) and muscle wasting (the loss of muscle mass caused by disease) 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. In fact, muscle homeostasis is dependent upon several anabolic and catabolic signals, including neurological, metabolic, hormonal, nutritional factors, and exercise (resistance training). In addition to loss of muscle, it has been recognized that dehydration in the elderly is a contributing risk factor adding to existing clinical conditions. Dehydration is the most common cause of hospitalization of nursing home residents. Therefore, the aim of this research program is to implement a multifaceted approach to investigate the aetiology of sarcopenia, muscle wasting and water homeostasis and to implement intervention strategies to ameliorate and/or reverse the age-related and/or disease-related loss of muscle mass with aging. 3. How does it relate to the National Program(s) and National Program Component(s) to which it has been assigned? This CRIS is related to the National Human Nutrition 107 program components: 1) relationship between diet, genetics, lifestyle and the risk of chronic diseases; 2) nutrient requirements; and 3) health promoting intervention strategies for targeted populations. It is not clear how diet composition and intake can best be altered to reduce, treat, or prevent sarcopenia. In addition, exercise, which is clearly able to treat sarcopenia and frailty of aging, also alters needs for some, but by no means all, nutrients. Furthermore, which nutrients could be used to improve physical performance in the elderly remains poorly defined. Because protein intake falls with age, it is possible that borderline protein deficiency is part of the cause of sarcopenia. Recent evidence suggests that aging is associated with a defect in the ability to synthesize muscle in response to a mixed protein-carbohydrate meal, suggesting that insulin resistance may be important to the development of sarcopenia. The results from this research program will lead to an improved understanding of the causes, consequences, prevention, and treatment of sarcopenia and muscle 4. What were the most significant accomplishments this past year? A. Most Significant Accomplishment: Given the high prevalence of diabetes in the elderly, searching for effective ways to improve metabolic control are crucial to maintain health and reduce the burden of this widely spread disease. We observed that 16 weeks of progressive resistance training resulted in skeletal muscle hypertrophy of both type I and type II muscle fibers in older individuals with poorly controlled diabetes. Additionally, engaging in resistance training in a supervised and safe manner improved performance- based physical function and muscle strength. Paralleling these findings, resistance training improved glycemic and metabolic control, and these parameters were significantly and preferentially associated with type I muscle fiber area. These data provide the first direct demonstration of a relationship between muscle fiber morphology, insulin-stimulated glucose uptake as measured by glycemic control, and resistance training status in skeletal muscle of untrained older adults with poorly controlled diabetes. B. Other Significant Accomplishments: In collaboration with the HNRCA Comparative Biology Unit, Nutrition, Exercise Physiology, and Sarcopenia Laboratory scientists developed a model of muscle injury triggered by subcutaneous deposition of turpentine, an irritant known to mobilize inflammatory cytokines. Models of inflammation are valuable to the study of sarcopenia because i) repair from muscle injury is impaired at old age, and ii) some mediators of inflammation (cytokines) contribute to muscle injury, and promote loss of muscle mass even in the absence of full blown inflammation. C. Significant Activities that Support Special Target Populations: None. D. Progress Report The Body Composition Laboratory developed a method for the rapid assessment of hydration status in nursing home residents based on field analysis of stable isotopes. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. The Nutrition, Exercise Physiology, and Sarcopenia Laboratory is noted for work indicating that progressive resistance training can reverse weakness and sarcopenia in various frail and chronically ill elderly populations, including nursing home patients, patients with arthritis, renal disease, heart disease, and diabetes. These laboratory findings have been widely reported in the scientific and lay press. Current research is refocusing the laboratory more on etiology of sarcopenia, as the intervention strategies have shown its efficacy, so that individual targets at the level of muscle (i.e. insulin resistance, anabolic and catabolic cytokines, and growth factors) can be intervened. The Body Composition Laboratory introduced a new concept for the assessment of nutritional status in the field. Using a combination of two simple measurements assesses the expansion of extracellular water space via bromide (Br) dilution for extracellular water (ECW) and portable X- ray absorptiometry for fat-free mass (FFM). The method provides the "frailty factor" defined as ECW/FFM. Preliminary results with human subjects at HNRCA show that the "frailty factor" is inversely related to the "quality of lean" score, which is the reference method for body composition nutritional status. The advantage of the method we introduced is that it is inexpensive, completely portable and provides real time results in the field. The Body Composition Laboratory has improved the fast neutron inelastic scattering method and expanded its design to include muscle and nitrogen measurements. The validation of dual photon absorptiometry against neutron inelastic scattering was completed. We will continue using this technique as the reference method for unbiased elemental body composition in human subjects. Applications to in vivo fat assessment of large animals are under discussion with our colleagues at USDA-Beltsville. 6. What do you expect to accomplish, year by year, over the next 3 years? This project is currently involved in the OSQR Panel Review Process for the Human Nutrition National Program 107. 7. 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 importance of progressive resistance training to promote optimal muscle hypertrophy, muscle function and improved quality of life has been communicated to the lay public. 8. List your most important publications in the popular press and presentations to organizations and articles written about your work. (NOTE: This does not replace your peer-reviewed publications listed below). a) ARS Magazine April 2003: The Crossroads of Nutrition and Culture, page 20; b) ARS Food Nutrition Research Briefs February 2003: (http://www.ars. usda.gov/is/np/fnrb/fnrb1002.htm) c) Reuters Health Information January 14, 2003: http://www.medscape.com/viewarticle/447596?mpid=8401 d) ARS news December 2002 STORY LEAD: Exercise Improves Diabetes Care among Hispanic Elders (English and Spanish versions)

Impacts
(N/A)

Publications

Ardern, C.I., Katzmarzyk, P.T., Janssen, I., Ross, R. Discrimination of health risk by combined body mass index and waist circumference. Obesity Research. 2003. v. 11. p. 135-142.
Castaneda, C., Layne, J., Munoz-Orians, L., Gordon, P.L., Walsmith, J., Foldvari, M., Roubenoff, R., Tucker, K.L., Nelson, M. A randomized control trial of progressive resistance exercise training in older adults with type 2 diabetes. Diabetes Care. 2002. v. 25(12). p. 2335-2341.
Bairos, L., Roubenoff, R., Kehayias, J.J., Dawson-Hughes, B. Comparison of lunar and hologic dual-energy x-ray absorptiometers (DXA) for whole and regional body composition. FASEB Journal. 2002. v. 16(5). Abstract No. 1024.
Castaneda, C., Gordon, P.L., Parker, R., Roubenoff, R., Levey, A.S. Resistance training reduces the underlying micro-inflammatory syndrome of chronic renal insufficiency. FASEB Journal. 2003. v. 17(4). Abstract No. 692.
Gordon PL, Vannier E, Roubenoff R, Castaneda C. Gender differences in relationships among adiposity, cytokines and clinical parameters in Hispanic Elders with type 2 diabetes. FASEB Journal 2003. v. 17(4). Abstract No.864.
Hughes, V.A., Zoico, E., Akos, R., Wood, M., Frontera, W.R., Fiatarone Singh, M.A., Roubenoff, R. Musculoskeletal endurance is associated with functional status in the elderly. The Gerontologist. 2002. v. 42(1). p. 359.
Kehayias, J.J., Sheahan, C., O'Neil, M., D'Alarcao, R. Portable x-ray absorptiometer caliper for in-vivo assessment of soft tissue composition. Acta Diabetologica. 2002 . v. 39(3). p. 136.
Kehayias, J.J., Valtuena, S., Sheahan, C., O'Neil, M. Validation of Bedside Methods for Assessing body composition and frailty in nursing home residents. The Gerontologist. 2002. v. 42. p. 241.
Vannier, E., Leite, H., Borggraefe, I., Hamada, E., Roubenoff, R. Identification of Novel 5'UTRs in Human and Rat Interleukin-15 Transcripts. Journal of Interferon and Cytokine Research. 2002. v. 22(suppl.1), p. S- 127.

Progress 10/01/01 to 09/30/02

Outputs
1. What major problem or issue is being resolved and how are you resolving it? This CRIS consists of the Nutrition, Exercise Physiology, and Sarcopenia and the Body Composition laboratories. The Nutrition, Exercise Physiology, and Sarcopenia Laboratory studies the interaction between nutrition and exercise in aging, especially as it relates to sarcopenia, the loss of muscle with age. This problem is addressed from several vantage points, using both human and animal models of muscle loss. The Body Composition Laboratory works to increase the understanding of mechanisms leading to the age-related loss of muscle mass and to develop appropriate interventions that will slow down or reverse this decline. Current studies laboratory examine: a) Healthy elderly women with sarcopenia and the response of single muscle cells to strength training; b) The feasibility of a school-based exercise and diet program in children to increase bone density and prevent osteoporosis later in life; c) Muscle cytokine gene expression in a rat model of inflammatory cachexia; d) The adequacy of the RDA for protein in sedentary and exercising elderly men; e) A novel mouse model of sarcopenia; f) The effect of dietary restriction on muscle loss in rats; g) The role of cytokines in predicting sarcopenia and death in the Framingham Heart Study; h) Development of a new, portable dual-energy absorptiometer, called microDXA, to measure sarcopenia in populations that cannot easily come to the laboratory; i) Validation of a field method for measuring extracellular water using plasma bromine. 2. How serious is the problem? Why does it matter? Sarcopenia is universal in the elderly, indicating that it is an age- related, rather than disease-related problem. Although high levels of physical activity can retard sarcopenia, it is seen even in Master athletes with age. Epidemiological data suggest that over 50 percent of adults over age 75 have measurable sarcopenia, and this is associated with increased risk of disability. In addition, the reduced protein stores inherent in sarcopenia leave the elderly with reduced ability to cope with illness or injury. Sarcopenia is tightly linked to osteopenia, disability, and institutionalization in the elderly. 3. How does it relate to the national Program(s) and National Program Component(s) to which it has been assigned? This research is conducted within the National Program 107 - Human Nutrition. This CRIS is most closely related to the Human Nutrition program components "Nutrient requirements" and the "Relationship between diet, genetics and lifestyle and the risk for chronic disease". It is not clear how diet composition and intake can best be altered to reduce, treat, or prevent sarcopenia. In addition, exercise, which is clearly able to treat sarcopenia and frailty of aging, also alters nutritional needs for some, but by no means all, nutrients. Furthermore, which nutrients could be used to improve physical performance in the elderly remain poorly defined. Because protein intake falls with age, it is possible that borderline protein deficiency is part of the cause of sarcopenia. Recent evidence suggests that aging is associated with a defect in the ability to synthesize muscle in response to a mixed protein-carbohydrate meal, suggesting that insulin resistance may be important to the development of sarcopenia. 4. What was your most significant accomplishment this past year? A. Single Most Significant Accomplishment during FY 2002: Elevated interleukin (IL)-6 and low insulin-like growth factor-I in serum, tumor necrosis factor-alpha production by white blood cells, and greater loss of lean body mass each independently predict mortality in elderly community-dwelling adults. This work was done in collaboration with the Framingham Heart Study and the Boston University School of Medicine. In additional work on IL-6 in muscle, scientists have discovered that muscle IL-6 gene expression is paradoxically lower in old men compared to young men after exercise, even though their serum IL-6 is higher. These findings suggest that IL-6 could have a dual role in sarcopenia, with basal levels too high in the elderly, but the response to stimulation too low to properly elevate muscle protein turnover. The close coordination among different cytokines in muscle from young men after exercise was not seen in the elderly, suggesting that aging causes loss of cytokine patterning, which may also account for the loss of appropriate muscle protein synthetic response with age. B. Other Significant Accomplishments: 1. In a collaboration with the HNRCA Comparative Biology Unit, Nutrition, Exercise Physiology and Sarcopenia laboratory scientists developed a novel model of sarcopenia in mice that emulates the type II fiber loss seen in humans, but does not require inducing inflammation or other noxious stimuli, as has been the case with the rat model to date. This is a very important breakthrough because it is the first model to show age- related loss of muscle in a susceptible mouse strain with little loss in a resistant strain. Such a model will be valuable in assessing potential treatments of sarcopenia in preclinical studies. 2. Continuing the development of field methods of assessing body composition, Dr. Joseph Kehayias of the Body Composition Laboratory was awarded a patent for the portable DXA instrument, microDXA (US Patent 6, 249,564 B1). This work was done with contracts to local machinists and engineering firms for specific parts. This instrument should yield the first unbiased measures of muscle mass that can be used in a field setting to assess sarcopenia, and is expected to be a major breakthrough in sarcopenia research. C. Significant Activities that Support Special Target Populations: None. D. Progress Report: The Body Composition Laboratory introduced a new concept for the assessment of nutritional status in the field. The expansion of extracellular water space is assessed by using a combination of two simple measurements: Bromide (Br) dilution for extracellular water and portable X-ray absorptiometry for fat-free mass. The method provides the "frailty factor" defined as ECW/FFM. Preliminary results with human subjects show that the "frailty factor" is inversely related to the "quality of lean" score, which is the reference method for body composition nutritional status. Several investigators have recognized the value of monitoring ECW space. However, bromide analysis, its calibration and validation have limited its practical applications. The advantage of this method is that it is inexpensive, completely portable and provides results in the field. The Body Composition Laboratory has improved the fast neutron inelastic scattering method and expanded its design to include muscle and nitrogen measurements. The validation of dual photon absorptiometry against neutron inelastic scattering was completed. Dr. J. Kehayias was awarded US patent Number 6,314,152 for this method/device on November 6, 2001. This technique will be used as the reference method for unbiased elemental body composition in human subjects. Two similar installations of this device are funded and are underway (at the USDA-CNRC in Houston and Columbia University - St Luke's Hospital in New York). Applications to in vivo fat assessment of large animals are under discussion with our colleagues at USDA-Beltsville. 5. Describe your major accomplishments over the life of the project, including their predicted or actual impact? The Nutrition, Exercise Physiology, and Sarcopenia Laboratory is noted for work indicating that progressive resistance training can reverse weakness and sarcopenia in various frail and chronically ill elderly populations, including nursing home patients, patients with arthritis, renal disease, and heart disease. These findings have been widely reported in the scientific and lay press. Current research is refocusing the laboratory more on etiology of sarcopenia, as the treatment issues have become more clear as a result of previous efforts, and on inventing better methods of measuring sarcopenia. 6. What do you expect to accomplish, year by year, over the next 3 years? The CRIS is currently in the midst of data collection for the projects listed under question 1, and expect this process to continue through the next 3 years. Year 1: Pursue supplementary funding for: a) A study of the role of IL-6 in sarcopenia in younger, healthier women (aged 70-75) than in our Framingham data (mean age 82); b) A multicenter trial of the effect of growth hormone and testosterone on muscle protein synthesis in frail elderly men; c) A study of the effect of diet and exercise on muscle cytokines and muscle protein synthesis; d) Preliminary studies using gene chip technology to identify muscle proteins important in the response to wasting and exercise; Year 2: e) Expansion of the HNRCA's neutron activation facility to include nitrogen and phosphorus; f) Validate traditional (total body water, bioimpedance) and new (microDXA, bromide) body composition methods against our reference techniques; g) Use field and reference body composition methods to study hydration status and frailty in the elderly. Year 3: h) Investigate the relationship between cognitive function, frailty and hydration status. Expand this protocol to include the use of a re- hydration process and measure its effectiveness using the portable instrumentation. i) Use the nursing home study to evaluate the ability of multi-frequency bioelectrical impedance to assess intra- and extra- cellular water compartments in this population. Full spectroscopic data is acquired for each volunteer. 7. What technologies have been transferred and to whom? When is the technology likely to become available to the end user (industry, farmer other scientist)? What are the constraints, if known, to the adoption durability of the technology? The methods used to promote optimal muscle hypertrophy using progressive resistance training have been published for the lay public by Dr. Nelson in her books, 'Strong Women Stay Young', Strong Women Stay Slim', 'Strong Women, Strong Bones' and most recently,'Strong Women and Men Beat Arthritis'. Dr. Kehayias was awarded US patent Number 6,314,152 for a method/device on November 6, 2001, which will allow transfer of the portable dual x-ray absorptiometry technology to interested users. 8. List your most important publications and presentations, and articles written about your work (NOTE: this does not replace your review publications which are listed below) Drs. Roubenoff, Nelson, and Economos have been interviewed my many media outlets, including national TV, radio, and print outlets. Nelson, M.E. , Baker, K.R., Roubenoff, R., Lindner, L. Strong Women and Men Beat Arthritis. New York: Putnam, 2002. 300 pages. Nelson, M.E. Monthly Column for Prevention Magazine. 2001-2002.

Impacts
(N/A)

Publications

Castaneda, C. In the literature: a nurse-delivered home exercise program for elderly individuals prevented falls but was costly. Nutrition in Clinical Care. 2001. v.4. p.269-270.
Castaneda, C., Gordon, P.L., Uhlin, K.L., Levey, A.S., Kehayias, J.J., Dwyer, J.T., Roubenoff, R., Fielding, R.A., Fiatarone Singh, M.A. Resistance training to counteract the catabolism of a low protein diet in patients with chronic renal insufficiency. A randomized, controlled trail. Annals of Internal Medicine. 2001. v.135. p.965-976.
Economos, C.D. Less exercise now, more disease later? The critical role of childhood exercise interventions in reducing chronic disease burden. Nutrition in Clinical Care. 2001. v. 4. p. 306-313.
Frontera, W.F., Hughes, V.A., Krivickas, L. S., Roubenoff, R. Contractile properties of aging skeletal muscle. International Journal of Sport Nutrition and Exercise Metabolism. 2001. v.11. p. S14-S18.
Jatoi, A., Daly, B.D.T., Hughes, M.S., Dallal, G.E., Kehayias, J., Roubenoff, R. Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure? Annals of Thoracic Surgery. 2001. v. 72. p. 348-351.
Roubenoff, R., Castaneda, C. Editorial. Understanding the dynamics of aging muscle. Journal of the American Medical Association. 2001. v.286. p. 1230-1231.
Zoico, E., Roubenoff, R. The role of cytokines in regulating protein metabolism and muscle function. Nutrition Reviews. 2002. v. 60. p. 39-51.
Castaneda, C., Layne J.E., Gordon, P.L., Huynh, T., Foldvari, M., Walsmith ,J., Munoz-Orians, L., Roubenoff, R., Nelson, M.E. Skeletal muscle hypertrophy in poorly controlled hispanic older adults with type 2 diabetes in response to progressive resistance exercise training. FASEB Journal 2002. v.16(4): Abstract p.A24.
Gordon, P.L., Vannier, E., Hamada, K., Witsell, A., Hurley, B.F., Roubenoff, R., Castaneda, C. Cytokine gene expression in skeletal muscle of Hispanic elders with type 2 diabetes. FASEB Journal. 2002. v.16(4): Abstract p.A396.
Kehayias, J.J., Sheahan, C.A., O'Neill, M. Body composition methodology for assessing the efficacy of pharmaceutical treatments of obesity. Obesity Research. 2001. v. 9(Suppl 3): Abstract p. 202S.
Kehayias, J.J., Sheahan, C.A., Waitekus, A.B., O'Neill, M. Body composition assessment as an outcome of nutritional intervention: validation of new rapid field methods. Annals of Nutrition and Metabolism. 2001. v. 45(suppl 1): Abstract p. 331.
Yamada, T., Vannier, E., Teutsch, A., Smith, D., Hamada, K., Hartman, W., Roubenoff R. A low protein diet modulates cytokine gene expression in skeletal muscles of rats performing physical activity. FASEB Journal 2002. v. 16(5 Part 2): Abstract p. A265.
Kehayias, J.J. Aging and body composition. Rosenberg, I.H., Sastre, A., editors. Vevey/S. Karger AG, Basel, Switzerland. Nutrition and Aging, first edition. 2002. p. 63-78.
Bairos, L., Roubenoff, R., Kehayias, J., Dawson-Hughes, B. Comparison of Lunar DPX-L and Hologic QDR-2000 dual-energy X-ray absorptiometers (DXA) for the evaluation of whole and regional body composition. FASEB Journal 2002. 16(5 Part 2): Abstract p. A1024.

Progress 10/01/00 to 09/30/01

Outputs
1. What major problem or issue is being resolved and how are you resolving it? The Nutrition, Exercise Physiology, and Sarcopenia Laboratory studies the interaction between nutrition and exercise in aging, especially as it relates to sarcopenia, the loss of muscle with age. This problem is approached from several vantage points, using both human and animal models of muscle loss. Current studies examine: a) healthy elderly women with sarcopenia and the response of single muscle cells to strength training; b) the feasibility of a school-based exercise and diet program in children as a means to increase bone density and prevent osteoporosis later in life; c) muscle cytokine gene expression in a rat model of inflammatory cachexia; d) the adequacy of the Recommended Dietary Allowances for protein in sedentary and exercising elderly men; e) a novel mouse model of sarcopenia; f) the role of exercise training in treating or preventing obesity in the elderly; g) the effect of dietary restriction on muscle loss in rats; h) the role of cytokines in predicting sarcopenia and death in the Framingham Heart Study. The laboratory is also i) developing a new, portable dual-energy absorptiometer, called microDXA, to measure sarcopenia in populations that cannot easily come to the laboratory; and j) validating a field method for measuring extracellular water using plasma bromine. 2. How serious is the problem? Why does it matter? Sarcopenia is universal in the elderly, indicating that it is an age-related, rather than disease-related problem. Although high levels of physical activity can retard sarcopenia, it is seen even in Master athletes with age. Epidemiologic data suggest that over 50 percent of adults over age 75 have measurable sarcopenia, and this is associated with increased risk of disability. In addition, the reduced protein stores inherent in sarcopenia leave the elderly with reduced ability to cope with illness or injury. Sarcopenia is tightly linked to osteopenia, disability, and institutionalization in the elderly. 3. How does it relate to the National Program(s) and National Component(s)? Our research is conducted within the national program 107- Human Nutrition is related to the program component "Nutrient requirements". It is unclear how diet composition and intake can best be altered to reduce, treat, or prevent sarcopenia. Exercise, which is used to treat sarcopenia and frailty of aging, also alters nutritional needs for some, but by no means all, nutrients. Which nutrients may be used to improve physical performance in the elderly remain poorly defined. Because protein intake falls with age, it is possible that borderline protein deficiency is part of the cause of sarcopenia. Recent evidence suggests that aging is associated with a defect in the ability to synthesize muscle in response to a mixed protein-carbohydrate meal, suggesting that insulin resistance may be important to the development of sarcopenia. 4. What were the most significant accomplishments this past year? A. Single most siginificant accomplishment during FY 2001: In collaboration with the Framingham Heart Study, it has found that the production of the cytokine interleukin-6 (IL-6) by peripheral blood mononuclear cells from elderly women predicts the rate of loss of lean body mass over the next two years. Cytokines are hormone like proteins involved in immune response regulation. In men, the major predictor of sarcopenia was insulin-like growth factor-I (IGF-I). These data indicate that there are sex differences in how sarcopenia is regulated, and that assessing a catabolic signal such as IL-6 may be important, offering a new direction for treatment and prevention. B. Other Significant Accomplishments: A novel model of sarcopenia in mice was developed that emulates the type II fiber loss seen in humans, but does not require inducing inflammation or other noxious stimuli, as has been the case with the rat model to date. This very important breakthrough is the first model to show age-related loss of muscle in a susceptible mouse strain with little loss in a resistant strain. Such a model will be valuable in assessing potential treatments of sarcopenia in preclinical studies. A patent was awarded for the portable dual x-ray absorptionmetry (DXA) instrument, microDXA (US Patent 6,249,564 B1). This instrument is being built through contracts to local machinists and engineering firms for specific components. This instrument should yield the first unbiased measures of muscle mass that can be used in a field setting to assess sarcopenia, and should be a major breakthrough in sarcopenia research. C. Significant accomplishments/activities that support special target populations: N/A. 5. Describe the major accomplishments over the life of the project including their predicted or actual impact. The laboratory is noted for its work indicating that progressive resistance training (PRT) can reverse weakness and sarcopenia in various frail and chronically ill elderly populations, including nursing home patients, and individuals with arthritis, renal disease, and heart disease. Our laboratory findings have been widely reported in the scientific and lay press. Current research is refocusing the laboratory more on the etiology of sarcopenia, as the treatment issues have become more clear as a result of previous efforts, and on inventing better methods of measuring sarcopenia. The results reported in response to question 4 and in the previous years' reports indicate that this change in direction is beginning to bear fruit. 6. What do you expect to accomplish, year by year, over the next 3 years? Over the next three years we will submit proposals for supplementary funding from the NIH or NRICGP for the following projects: a) study of the role of IL-6 in sarcopenia in younger, healthier women (aged 70-75) than our Framingham subjects (mean age 82); b) a multi-center trial of the effect of growth hormone and testosterone on muscle protein synthesis in frail elderly men; c) a study of the effect of diet and exercise on muscle cytokines and muscle protein synthesis; d) preliminary studies using gene chip technology to identify muscle proteins important in the response to wasting and exercise; e) expansion of the neutron activation facility at the HNRCA to include nitrogen and phosphorus; f) validatation of traditional (total body water, bioimpedance) and new (microDXA, bromide) body composition methods against our reference techniques; and g) the use our field and reference body composition methods to study hydration status and frailty in the elderly. 7. 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 & durability of the technology product? The methods used to promote optimal muscle hypertrophy using PRT have been published for the lay public by Dr. Nelson in her books, 'Strong Women Stay Young', Strong Women Stay Slim', and most recently, 'Strong Women, Strong Bones'. Drs. Roubenoff, Nelson, and Economos have been interviewed my many media outlets, including national television, radio, and print outlets. Dr. Kehayias was awarded a patent (US Patent 6,249,564 B1) which will allow transfer of the portable DXA technology to interested users. 8. List your most important publications in the popular press (no abstracts) and presentations to non-scientific organizations and articles written about your work (NOTE: this does not replace your peer-reviewed publications which are listed below) Nelson, M.E., with Judy Knipe, Strong Women Eat Well. Putnam Books, NY, NY. 2001. 268 pp. Nelson, M.E., Monthly Column for Prevention Magazine. 2001. Strength Training's 7% Solution. USA Today. July 12, 2001.

Impacts
(N/A)

Publications

Castaneda, C., Munoz-Orians, L., Layne, J., Roubenoff, R., Nelson, M., Tucker, K. Improved glycemic control in Hispanic elders with type 2 diabetes: effects of diet and resistance exercise training. Federation of American Societies for Experimental Biology Journal. 2001. v. 15(5). Abstract p. A726.
Hays, N.P., Bathalon, G.P., Roubenoff, R., Roberts, S.B. Eating behavior correlates of health disorders in women aged 55-65 years. Federation of American Societies for Experimental Biology Journal. 2001. V. 15(4). Abstract p. A399.
Kehayias, J.J., Sheahan, C.A., Waitekus, A.B., O'Neill, M., Stamatelatos, I.E. Field methods for body composition: validation of rapid extracellular water space assessment against instrumental neutron activation. Federation of American Societies for Experimental Biology Journal. 2001. v 15(4). Abstract p. A252.
McCrory, M.A., Roubenoff, R., Fuss, P.J., Munoz-Orians, L., Castaneda, C. Comparison of methods for measuring body composition responses to progressive resistance training in Hispanic elders with type 2 diabetes. Federation of American Societies for Experimental Biology. 2001. v. 15(4). Abstract p. A252.
Roubenoff, R., Lundgren, N., Snydman, L., Roberts, S. Energy metabolism in rheumatoid arthritis: doubly labeled water analyses. Arthritis Research Conference. 2001. Abstract p. 33.
Roubenoff, R., Hamada. K., Vannier, E., Cannon, J.G., Edwards, C.K., Smith, D.E., Yamada, T. Cytokine gene expression by skeletal muscle in adjuvant arthritis. Arthritis Research Conference. 2001. Abstract p. 102.
Roubenoff, R., Abad, L.W., Parker, R.C. Cytokine responses differ by wasting status and compartment in patients with HIV infection and healthy controls. Federation of American Societies for Experimental Biology Journal. 2001. v. 15(5 Pt 1). Abstract P. A64.
Walsmith, J., Snydman, L., Roubenoff, R. Tumor necrosis factor-a (TNF) production is associated with less body cell mass in rheumatoid arthritis [RA]. Arthritis and Rheumatism. 2000. v. 43(9). Abstract p. S80.
Roubenoff, R. Body composition in starvation, inflammation, and aging: the relationship among wasting, cachexia, and sarcopenia. Pierson, R.N., editor. Springer, New York, NY. Quality of the Body Cell Mass: Body Composition in the Third Millennium. 2000. p. 312-320.
Bermudez, O.S., Valtueaa, S., Castaneda, C., Waitekus, A.B., Sheahan, C.A., Tucker, K.L., Kehayias, J.J. Accuracy of bioelectrical impedance for measurements of body composition in Hispanic elderly women. Federation of American Societies for Experimental Biology Journal. v. 15(4). Abstract p. A1002.
Castaneda, C., Munoz-Orians, L., Layne, J., Walsmith, J., Foldvari, M., Roubenoff, R., Tucker, K.L., Nelson, M. A randomized trial of resistance exercise training to improve glycemic control on Hispanic elders with diabetes. Diabetes. 2001. v. 50(Suppl. 2): Abstract p. 221.
Baker, K.R., Nelson, M.E., Felson, D.T., Layne, J.E., Sarno, R., Roubenoff, R. The efficacy of home-based, progressive strength training in older adults with knee osteoarthritis. Journal of Rheumatology. 2001. v. 28. p. 1655-1665.
Castaneda, C. Protein restriction in renal disease. Nutrition in Clinical Care. 2001. v. 4. p. 103-112.
Economos, C., Brownson, S., DeAngelis, M., Foerster, S., Tucker Foreman, C., Kumanyika, S., Pate, R. What lessons have been learned from other attempts to guide social change? Nutrition Reviews. 2001. v. 9. p. 40-56.
Frontera, W.R., Suh, D., Krivickas, L., Hughes, V.A., Goldstein, R., Roubenoff, R. Skeletal muscle fiber quality in older men and women. Amercian Journal of Physiology. 2000. v. 279. p. C611-C618.
Hausdorff, J.M., Nelson, M.E., Kaliton, D., Layne, J.E., Bernstein M.J., Nuernberger, A., Fiatarone Singh, M.A. The etiology and plasticity of gait instability in older adults: a randomized controlled trial of exercise. Journal of Applied Physiology. 2001. v. 90. p. 2117-2129.
Hughes, V. A., Frontera, W.R., Wood, M., Evans, W.J., Dallal, G.E., Roubenoff, R. Fiatarone Singh, M.A. Longitudinal muscle function changes in older adults: Influence of muscle mass, physical activity and health. Journals of Gerontology Biological Sciences and Medical Sciences. 2001. v. 56A. p. B209-B217.
Krivickas, L.S., Suh, D., Wilkins, J., Hughes, V.A., Roubenoff, R., Frontera, W.R. Age- and Gender-related differences in maximum shortening velocity of skeletal muscle fibers. American Journal of Physical Medicine and Rehabilitation. 2001. v. 80. p. 447-455.
Rall, L.C., Roubenoff, R. Benefits of exercise for patients with rheumatoid arthritis. Nutrition in Clinical Care. 2000. v. 3. p. 209-215.
Roubenoff, R., Forman, D. Exercise in the management of heart failure. Nutrition in Clinical Care. 2000. v. 3. p. 225-229.
Roubenoff, R. Sarcopenic obesity: Does muscle loss cause fat gain? Lessons from rheumatoid arthritis and osteoarthritis. Annals of the New York Academy of Sciences. 2000. v. 904. p. 553-557.
Roubenoff, R., Hughes, V.A. Nelson, M.E., Morganti, C.M., Kehayias, J.J., Fiatarone Singh, M.A. Roberts, S. The effect of gender and body composition method on the apparent decline in lean-mass adjusted resting metabolic rate with age. Journals of Gerontology Biological and Medical Sciences. 2000. v. 55A. p. M757- M760.
Roubenoff, R. Sarcopenia: a major modifiable cause of frailty in the elderly. Journal of Nutrition and Health Aging. 2000. v. 4. p. 140-142.
Roubenoff, R., Hughes, V.A. Sarcopenia: current concepts. Journals of Gerontology Biological and Medical Sciences. 2000. v. 55A. p. M716-M724.
Roubenoff, R. Origins and clinical relevance of sarcopenia. Canadian Journal of Applied Physiology. 2001. v. 2B. p. 78-90.
Sacheck, J.M., Roubenoff, R. Nutritional needs of the female athlete. Sports in Primary Care. 2001. v. 1. p. 17-20.
Valtueaa S., Kehayias J.J. Determinacian de la masa grasa corporal in vivo: de las t cnicas bicompartimentales al an#lisis de activatcion de neutrones y la absorciometraa de rayos X de doble energaa (DXA) (Measurement of body fat mass in vivo: from two-compartment techniques to neutron activation analysis and DXA). Medicina Clinica. 2001. v. 116. p. 590-597.
Fiatarone-Singh, M.A. Soft tissue response to exercise in the elderly. Maffulli, N., Ming Chan, K., Macdonald, R., Malina, R.M., Parker, A.W., editors. Harcourt Publishers Limited, London. Sports Medicine for Specific Ages and Abilities. 2001. p. 263-274.
Kehayias, J.J. The elemantal partition analysis approach to body composition: possibilities for future studies. Pierson R.N., editor. Springer, New York. Quality of the Body Cell Mass: Body Composition in the Third Millennium. 2000. p. 166-174.
Kehayias, J.J. Medical applications of in vivo neutron inelastic scattering and neutron activation analysis: technical similarities to detection of explosives and contraband. Duggan, J.L., Morgan, I.L., editors. AIP, Melville, NY. Application of Accelerators in Research and Industry. 2001. v. 576. p. 873-876.