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Research Project: Sarcopenia, Nutrition, and Physical Activity

Location: Jean Mayer Human Nutrition Research Center On Aging

2018 Annual Report


1a. Objectives (from AD-416):
LAB NAME: Nutrition, Exercise Physiology, and Sarcopenia 1. Characterize the mechanisms associated with nutritional and contraction-related mediators of anabolic resistance associated with advancing age and/or obesity in animal models and humans. 2. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on physical functioning in older adults with chronic kidney disease or limited mobility. 3. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on cognitive functioning in older adults with chronic kidney disease or limited mobility.


1b. Approach (from AD-416):
LAB NAME: Nutrition, Exercise Physiology, and Sarcopenia Sarcopenia, the age-associated loss in skeletal muscle mass and function, is a contributing factor to the observed declines in physiological capacity and physical functioning with advancing age. The overall theme of this project will be to conduct basic and clinical studies focused on the identification, evaluation, and understanding of nutritional and physical activity interventions that possess anabolic properties in skeletal muscle and have the potential to prevent or reverse impaired motor and cognitive performance and/or physical dysfunction in older individuals. Our basic research program will focus on understanding the molecular mechanisms associated with age-related anabolic resistance in skeletal muscle. These basic studies will be uniquely synergized with our clinical/translational studies designed to evaluate the potential efficacy of nutritional and exercise interventions in older adults. Our proposed clinical studies will further seek to understand the role of structured physical activity and nutritional supplementation on changes in physical function and disability in older adults with mobility limitations as a consequence of anabolic resistance and/or sarcopenia. In addition, we will also examine the role of structured physical activity on changes in cognition and the role of physical activity on dementia risk. 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, physical activity) may accelerate our ability to translate these findings to aging people.


3. Progress Report:
We have made substantial progress on all objectives outlined in our project plan. In the current project year, we have substantially or fully met all of our approved milestones. Work on Objectives: 1. Characterize the mechanisms associated with nutritional and contraction-related mediators of anabolic resistance associated with advancing age and/or obesity in animal models and humans, 2. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on physical functioning in older adults with chronic kidney disease or limited mobility, and 3. Determine the effects of structured, long term interventions of aerobic walking and resistance physical activity on cognitive functioning in older adults with chronic kidney disease or limited mobility, is all ongoing. Our major focus for objective 1 has been to refine our capacity to perform experiments using skeletal muscle cell culture models. We have now optimized our procedures and can consistently raise primary cultures (myoblasts and myotubes) from human skeletal muscle biopsy specimens. We have now collected muscle samples and extracted muscle stem cells from young, healthy older, and older with sarcopenic men and women. These samples are now being used to examine the effects of specific skeletal muscle microRNA on measures of skeletal muscle protein synthesis and growth capacity. In addition, we continue to investigate the effects of specific nutrients (carnitine, creatine, and varying chain length fatty acids) on skeletal muscle protein synthesis and growth capacity using these same cell culture systems. For Objectives 2 and 3, the proposed clinical trials are completed and results are in the process of being analyzed and published. In addition, we have completed new work on the study of the gut microbiome and the role that gut microbiome-derived metabolites play on the age-related loss of skeletal muscle mass and function, sarcopenia.


4. Accomplishments
1. Non-invasive marker found to identify loss of skeletal muscle mass in older adults. Age-related loss of muscle mass and function, a condition known as sarcopenia, affects the mobility of older adults and often leads to frailty and loss of independence. ARS-funded researchers in Boston, Massachusetts tested the blood levels of specific genes known as circulating microRNAs in a small group of healthy young and older men and found significant differences in their concentrations between the groups. The results showed that measures of blood levels of microRNA following resistance exercise be an important marker of the muscle building capacity of exercise. These new findings may lead to a non-invasive way to predict the risk of sarcopenia in older adults and lead to new treatments for the recovery of muscle mass or slowing of its loss.

2. Adding modest amount of moderate exercise in later years improves mobility of older adults. As people age and become less active they lose mobility, leading to falls, hip fractures and often loss of independence. ARS-funded researchers in Boston, Massachusetts have determined that people in their 70s and 80s who have previously been inactive can improve their ability to move and function by walking at a moderate speed for at least 48 minutes a week. The researchers were part of the Lifestyle Interventions and Independence for Elders (LIFE) study, a large multicenter randomized controlled trial designed to compare the effects of a moderate intensity physical activity program with a successful aging health education program. They analyzed data from 1,635 inactive people age 70 to 89 who were at high risk for conditions that would reduce their mobility. The researchers found participants in the exercise group increased their walking speed and distance and experienced less decline in mobility than study participants enrolled in a health education program that did not include walking. Influencing older adults to walk at least 1 hour a week may reduce healthcare costs and improve the quality of life for millions.


Review Publications
Cesari, M., Fielding, R.A., Benichou, O., Bernabei, R., Bhasin, S., Guralnik, J.M., Jette, A., Landi, F., Pahor, M., Rodriguez-Manas, L., Rolland, Y., Roubenoff, R., Sinclair, A.J., Studenski, S., Travison, T., Vellas, B. 2015. Pharmacological intervention in frailty and sarcopenia: report by the International Conference on Frailty and Sarcopenia Research Task Force. The Journal of Frailty and Aging. 4(3):114-120. https://doi.org/10.14283/jfa.2015.64.
Margolis, L., Rivas, D.A., Berrone, M., Ezzyat, Y., Young, A.J., McClung, J.P., Fielding, R.A., Pasiakos, S.M. 2016. Prolonged calorie restriction downregulates skeletal muscle mTORC1 signaling independent of dietary protein intake and associated microRNA expression. Frontiers in Physiology. https://doi.org/10.3389/fphys.2016.00445.
Margolis, L., Rivas, D.A., Pasiakos, S., McClung, J.P., Ceglia, L., Fielding, R.A. 2017. Upregulation of circulating myomiR following short-term energy restriction is inversely associated with whole body protein synthesis. American Journal of Physiology - Regulatory Integrative & Comparative Physiology. 313(3):R298-R304. https://doi.org/10.1152/ajpregu.00054.2017.
Margolis, L., Lessard, S., Ezzyat, Y., Fielding, R.A., Rivas, D.A. 2016. Circulating microRNA are predictive of aging and acute adaptive response to resistance exercise in men. Journal of Gerontology Biological Science. https://doi.org/10.1093/gerona/glw243.
Hau, C., Reid, K.F., Wong, K.F., Chin, R.J., Botto, T.J., Eliasziw, M., Bermudez, O.I., Fielding, R.A. 2015. Collaborative evaluation of the healthy habits program: an effective community intervention to improve mobility and cognition of Chinese older adults living in the U.S. Journal of Nutrition Health and Aging. 20(4):391-397. https://doi.org/10.1007/s12603-015-0623-8.
Pojednic, R., Ceglia, L., Olsson, K., Gustafsson, T., Lichtenstein, A.H., Dawson-Hughes, B., Fielding, R.A. 2014. Effects of 1,25-dihydroxyvitamin D3 and vitamin D3 on the expression of the vitamin D receptor in human skeletal muscle cells. Calcified Tissue International. 96(3):256-263.
Henderson, R.M., Lovato, L., Miller, M.E., Fielding, R.A., Church, T.S., Newman, A.B., Buford, T.W., Pahor, M., McDermott, M.M., Stafford, R.S., Lee, D.S., Kritchevsky, S.B. 2016. Effect of statin use on mobility disability and its prevention in at-risk older adults: the LIFE study. Journal of Gerontology Medical Science. https://doi.org/10.1093/gerona/glw057.
Margolis, L., Rivas, D.A., Ezzyat, Y., Gaffney-Stomberg, E., Young, A.J., McClung, J.P., Fielding, R.A., Stefan, P.A. 2016. Calorie restricted high protein diets downregulate lipogenesis and lower intrahepatic triglyceride concentrations in male rats. Nutrients. 8(9):E571. https://doi.org/10.3390/nu8090571.
King, A., Salvo, D., Banda, J.A., Ahn, D.K., Chapman, J.E., Gill, T., Fielding, R.A., Demons, J., Tudor-Locke, C., Rosso, A., Pahor, M., Frank, L.D. 2016. Preserving older adults' routine outdoor activities in contrasting neighborhood environments through a physical activity intervention. Preventive Medicine. 96:87-93. https://doi.org/10.1016/j.ypmed.2016.12.049.
Corcoran, M.P., Nelson, M.E., Sacheck, J.M., Reid, K.F., Kirn, D., Fielding, R.A., Folta, S.C. 2015. Recruitment of mobility limited older adults into a facility-led exercise-nutrition study: the effect of social involvement. Gerontologist. 56(4):669-676. https://doi.org/10.1093/geront/gnv018.
Gill, T.M., Guralnik, J.M., Pahor, M., Church, T.S., Fielding, R.A., King, A.C., Marsh, A.P., Newman, A.B., Pellegrini, C.A., Chen, S., Allore, H.G., Miller, M. 2016. Effect of structured physical activity on overall burden and transitions between states of major mobility disability in older persons: secondary analysis of a randomized trial. Annals Of Internal Medicine. 165(12):833-840.
Bann, D., Hire, D., Manini, T., Cooper, R., Botoseneanu, A., McDermott, M.M., Pahor, M., Glynn, N.W., Fielding, R.A., King, A.C., Church, T., Ambrosius, W.T., Gill, T. 2015. Light intensity physical activity and sedentary behavior in relation to body mass index and grip strength in older adults: cross-sectional findings from the Lifestyle Interventions and Independence for Elders (LIFE) study. PLoS One. 10(2):e0116058. https://doi.org/10.1371/journal.pone.0116058.
Newman, A.B., Dodson, J.A., Church, T.S., Buford, T.W., Fielding, R.A., Kritchevsky, S.B., Beavers, D.P., Pahor, M., Stafford, R.S., Szady, A.D., Ambrosius, W.T., McDermott, M. 2016. Cardiovascular events in a physical activity intervention compared with a successful aging intervention: The LIFE Study randomized trial. The Journal of the American Medical Association: Cardiology. 1(5):568-574.
Mavros, Y., O'Neill, E., Connerty, M., Bean, J.F., Broe, K., Kiel, D.P., Maclean, D., Taylor, A., Fielding, R., Fiatarone-Singh, M.A. 2015. Oxandrolone augmentation of resistance training in older women: a randomized trial. Medicine and Science in Sports and Exercise. https://doi.org/10.1249/MSS.0000000000000690.
Aubertin-Leheudre, M., Anton, S.D., Beavers, D.P., Manini, T.M., Fielding, R.A., Newman, A., Church, T., Kritchevsky, S.B., Conroy, D., McDermott, M.M., Botoseneanu, A., Hauser, M.E., Pahor, M. 2017. Dynapenia and metabolic health in obese and nonobese adults aged 70 years and older: The LIFE Study. Journal of the American Medical Directors Association - Post-Acute and Long Term Care Medicine. 18(4):312-319.
Evans, M., Guthrie, N., Pezzullo, J., Sanli, T., Fielding, R.A., Bellamine, A. 2017. Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study. Nutrition and Metabolism. 14:7. https://doi.org/10.1186/s12986-016-0158-y.
Kheirkhahan, M., Tudor-Locke, C., Axtell, R., Buman, M., Fielding, R.A., Glynn, N.W., Guralnik, J.M., King, A.C., White, D.K., Miller, M.E., Siddique, J., Brubaker, P.H., Rejeski, W., Ranshous, S., Pahor, M., Ranka, S., Manini, T. 2016. Actigraphy features for predicting mobility disability in older adults. Physiological Measurement. 37(10):1813-1833.
O Hartaigh, B., Pahor, M., Buford, T.W., Dodson, J.A., Forman, D.E., Gill, T. 2014. Physical activity and resting pulse rate in older adults: findings from a randomized controlled trial. American Heart Journal. 168(4):597-604. https://doi.org/10.1016/j.ahj.2014.07.024.
Fitzgerald, J.D., Johnson, L., Ambrosius, W.T., Anton, S.D., Dodson, J.A., Marsh, A.P., McDermott, M.M., Nocera, J.R., Tudor-Locke, C., White, D.K., Yank, V., Pahor, M., Manini, T., Buford, T. 2015. Association of objectively measured physical activity with cardiovascular risk in mobility-limited older adults. Journal of the American Heart Association. 4:e001288. https://doi.org/10.1161/JAHA.114.001288.
Pojednic, R., Ceglia, L., Lichtenstein, A.H., Dawson-Hughes, B., Fielding, R.A. 2014. Vitamin D receptor protein is associated with interleukin-6 in human skeletal muscle. Endocrine. 49(2):512-520. https://doi.org/10.1007/s12020-014-0505-6.
Espeland, M.A., Newman, A.B., Sink, K., Gill, T.M., King, A.C., Miller, M.E., Guralnik, J., Katula, J., Church, T., Manini, T., Reid, K.F., McDermott, M.M. 2015. Associations between ankle-brachial index and cognitive function: results from the Lifestyle Interventions and Independence for Elders trial. Journal of the American Medical Directors Association - Post-Acute and Long Term Care Medicine. 16(8):682-689. https://doi.org/10.1016/j.jamda.2015.03.010.
Fielding, R.A., Travison, T.G., Kirn, D.R., Koochek, A., Reid, K.F., Von Berens, A., Zhu, H., Folta, S.C., Sachek, J.M., Nelson, M.E., Liu, C., Aberg, A.C., Nydahl, M., Lilja, M., Gustafsson, T., Cederholm, T. 2017. Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults: results from the VIVE2 randomized trial. Journal of Nutrition Health and Aging. 21(9):936-942. https://doi.org/10.1007/s12603-017-0936-x.
Cocoran, M., Nelson, M.E., Sacheck, J., Reid, K.F., Kirn, D., Fielding, R.A., Chui, K.K., Folta, S.C. 2017. Efficacy of an exercise and nutritional supplement program on physical performance and nutritional status in older adults with mobility limitations residing at senior living facilities. Journal of Aging and Physical Activity. 25(3):453-463. https://doi.org/10.1123/japa.2016-0173.
Corbett, D.B., Rejeski, J.W., Tudor-Locke, C., Glynn, N.W., Kritchevsky, S.B., McDermott, M., Church, T., Fielding, R.A., Gill, T.M., King, A.C., Miller, M.E., Chen, H., Pahor, M., Manini, T. 2017. Social participation modifies the effect of a structured physical activity program on major mobility disability among older adults: results from the LIFE study. Journals of Gerontology. https://doi.org/10.1093/geronb/gbx051.
Kirn, D., Koochek, A., Reid, K.F., Von Berens, A., Travison, T.G., Folta, S., Sacheck, J., Nelson, M., Liu, C., Phillips, E., Aberg, A.C., Nydahl, M., Gustafsson, T., Cederholm, T., Fielding, R.A. 2015. The vitality, independence, and vigor in the elderly 2 study (VIVE2): design and methods. Contemporary Clinical Trials. 43:164-171. https://doi.org/10.1016/j.cct.2015.06.001.
Laussen, J.C., Kowaleski, C., Martin, K., Hickey, C., Fielding, R.A., Reid, K.F. 2016. Disseminating a clinically effective physical activity program to preserve mobility in a community setting for older adults. The Journal of Frailty and Aging. 5(2):82-87. https://doi.org/10.14283/jfa.2016.94.
Rejeski, W.J., Rushing, J., Guralnik, J.M., Ip, E.H., King, A.C., Manini, T.M., Marsh, A.P., McDermott, M.M., Fielding, R.A., Newman, A.B., Tudor-Locke, C., Gill, T.M. 2015. The MAT-sf: identifying risk for major mobility disability. Journal of Gerontology Medical Science. 70(5):641-646. https://doi.org/10.1093/gerona/glv003.
Cesari, M., Vellas, B., Hsu, F., Newman, A.B., Doss, H., King, A.C., Manini, T.M., Church, T., Gill, T.M., Miller, M., Pahor, M.S. 2015. A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. Journals of Gerontology. 70(2):216-222.
Trombetti, A., Hars, M., Hsu, F., Reid, K.F., Church, T.S., Gill, T.M., King, A.C., Liu, C.K., Manini, T.M., McDermott, M.M., Newman, A.B., Rejeski, J.W., Guralnik, J.M., Pahor, M., Fielding, R.A. 2018. Effect of physical activity on frailty: secondary analysis of a randomized controlled trial. Annals Of Internal Medicine. 168(5):309-316. https://doi.org/10.7326/M16-2011.
Marsh, A.P., Applegate, W.B., Guralnik, J.M., Rejeski, J.W., Church, T.S., Fielding, R.A., Gill, T.M., King, A.C., Kritchevsky, S.B., Manini, T.M., McDermott, M.M., Newman, A.B., Stowe, C.L., Walkup, M.P., Pahor, M., Miller, M.E. 2016. Hospitalizations during a physical activity intervention in older adults at risk of mobility disability: analyses from the lifestyle interventions and independence for elders randomized clinical trial. Journal of the American Geriatrics Society. (64)5:933-943. https://doi.org/10.1111/jgs.14114.
Englund, D.A., Kirn, D., Koochek, A., Zhu, H., Travison, T.G., Reid, K.F., Von Berens, A., Melin, M., Cederholm, T., Gustafsson, T., Fielding, R.A. 2017. Nutritional supplementation with physical activity improves muscle composition in mobility-limited older adults, The VIVE2 Study: a randomized, double-blind, placebo-controlled trial. Journal of Gerontology Biological Science. 73(1):95-101. https://doi.org/10.1093/gerona/glx141.
Von Berens, A., Koocheck, A., Nydahl, M., Fielding, R.A., Gustafsson, T., Kirn, D.R., Cederholm, T., Sodergren, M.H. 2018. "Feeling more self-confident, cheerful, and safe". Experiences from a health-promoting intervention in community dwelling older-adults- a qualitative study. Journal of Nutrition Health and Aging. 22(4):541-548. https://doi.org/10.1007/s12603-017-0981-5.
Santanasto, A.J., Glynn, N.W., Lovato, L.C., Blair, S.N., Fielding, R.A., Gill, T.M., Guralnik, J.M., Hsu, F., King, A.C., Strotmeyer, E.S., Manini, T.M., March, A.P., McDermott, M.M., Goodpaster, B.H., Pahor, M., Newman, A.B. 2017. Effect of physical activity versus health education on physical function, grip strength and mobility. Journal of American Geriatric Society. 65(7):1427-1433. https://doi.org/10.1111/jgs.14804.
Wang, C., Schmid, C.H., Fielding, R.A., Harvey, W.F., Reid, K.F., Price, L., Driban, J.B., Kalish, R., Rones, R., McAlindon, T. 2018. Effect of tai chi versus aerobic exercise for fibromyalgia: comparative effectiveness randomized controlled trial. The BMJ. 360:k851. https://doi.org/10.1136/bmj.k851.
Fielding, R.A., Guralnik, J.M., King, A.C., Pahor, M., McDermott, M.M., Tudor-Locke, C., Manini, T.M., Glynn, N.W., Marsh, A.P., Axtell, R.S., Hsu, F., Rejeski, W. 2017. Dose of physical activity, physical functioning and disability risk in mobility-limited older adults: results from the LIFE study randomized trial. PLoS One. 12(8):e0182155. https://doi.org/10.1371/journal.pone.0182155.
Henderson, R.M., Miller, M.E., Fielding, R.A., Gill, T.M., Glynn, N.W., Guralnik, J.M., King, A., Newman, A.B., Manini, T.M., Marsh, A.P., Pahor, M., McDermott, M.M., Rejeski, J., Tudor-Locke, C., Kritchevsky, S. 2018. Maintenance of physical function 1 year after exercise intervention in at-risk older adults: follow-up from the LIFE study. Journal of Gerontology Medical Science. 73(5):688-694. https://doi.org/10.1093/gerona/glx231.
Cruz-Jentoft, A.J., Landi, F., Schneider, S.M., Zuniga, C., Arai, H., Boirie, Y., Chen, L., Fielding, R.A., Martin, F.C., Michel, J., Sieber, C., Stout, J.R., Studenski, S.A., Vellas, B., Woo, J., Zamboni, M., Cederholm, T. 2014. Prevalence of and interventions for sarcopenia in ageing adults - a systematic review report of the international sarcopenia initiative (EWGSOP and IWGS). Age and Ageing. 43:748-759. https://doi.org/10.1093/ageing/afu115.
Wang, C., Iversen, M.D., McAlindon, T., Harvey, W.F., Wong, J.B., Fielding, R.A., Driban, J.B., Price, L., Rones, R., Gamache, T.C., Schmid, C. 2014. Assessing the comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: design and rationale for a randomized trial. BMC Complementary and Alternative Medicine. 14:333. https://doi.org/10.1186/1472-6882-14-333.
Vaz Fragoso, C.A., Hsu, F., Brinkley, T., Church, T., Liu, C., Manini, T., Newman, A.B., Stafford, R.S., McDermott, M.M., Gill, T.M. 2014. Combined reduced forced expiratory volume in 1 second (FEV1) and peripheral artery disease in sedentary elders with functional limitations. Journal of the American Medical Directors Association - Post-Acute and Long Term Care Medicine. 15(9):665-670. https://doi.org/10.1016/j.jamda.2014.05.008.