Prevention of age-associated musculoskeletal loss by n-3 fatty acids

n-3 脂肪酸预防与年龄相关的肌肉骨骼损失

• 批准号: 7893916
• 负责人: MD MIZANUR RAHMAN
• 金额: $ 12.27万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7893916
• 关键词: Adenosine; Adult; Advisory Committees; Age; Aging; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Antioxidants; Applications Grants; Area; Arthritis; Atherosclerosis; Attenuated; Binding; Biochemical Markers; Biology; Biology of Aging; Biomechanics; Bone Density; Bone Resorption; Bone remodeling; Breeding; Caloric Restriction; Cardiovascular Diseases; Cells; Chronic Disease; Clinical; Clinical Trials; Comparative Biology; Complex; Corn Oil; Data; Deterioration; Development Plans; Diabetes Mellitus; Disease; Drug Prescriptions; Dual-Energy X-Ray Absorptiometry; Elderly; Electron Transport; Elements; Ensure; Enzymes; Equilibrium; FDA approved; Fall prevention; Fatty Acids; Fatty acid glycerol esters; Female; Femur; Fiber; Fish Oils; Fracture; Funding; Gene Expression; Genes; Goals; Grant; Health; Human; Hypertriglyceridemia; Infection; Inflammation; Inflammatory; Institutes; International; Iron; Journals; Knowledge; Leg; Life; Life Support Care; Linoleic Acids; Liver; Longevity; Malignant Neoplasms; Malnutrition; Mammals; Materials Testing; Measures; Mediating; Membrane; Membrane Potentials; Menopause; Mentors; Metabolic syndrome; Minerals; Mitochondria; Monitor; Mus; Muscle; Muscle Fibers; Muscle function; Musculoskeletal; Musculoskeletal System; Nuclear Magnetic Resonance; Obesity; Omega-3 Fatty Acids; Organism; Osteogenesis; Osteopenia; Osteoporosis; Oxidation-Reduction; Oxidative Stress; Paper; Population; Porosity; Postmenopause; Predisposition; Prevention; Process; Production; Property; Publishing Peer Reviews; Reactive Oxygen Species; Reporting; Research; Research Personnel; Resources; Role; Safflower Oil; Scientist; Serum; Staining method; Stains; Testing; Therapeutic; Tissues; Training; Training and Education; Transgenic Organisms; Translational Research; Vascular Diseases; Vitamins; Water; Work; Writing; Yeasts; age group; age related; aging population; attenuation; bone; bone health; bone loss; bone mass; bone quality; bone strength; bone turnover; career; career development; cytokine; diabetic; dietary restriction; fall risk; feeding; functional decline; functional improvement; grasp; healthy aging; improved; indexing; inorganic phosphate; interest; male; muscle form; muscle strength; new technology; oxidative damage; prevent; prophylactic; protective effect; public health relevance; reproductive; respiratory; sarcopenia; skills; spine bone structure; symposium

DESCRIPTION (provided by applicant): Aging is associated with increased inflammation and oxidative stress leading to progressive decline in musculoskeletal tissue mass, quality and function which increases the risk of falls and fractures in the elderly. Both n-3 fatty acids (FA) and calorie restriction (CR) are anti-inflammatory and anti-oxidative. CR improves muscle mass, quality and function and n-3 FA improves bone mineral density (BMD) and muscle function and prevents bone loss. We observed increased hind leg lean mass in n-3 FA fed mice. However, 40% CR is associated with increased bone loss. Therefore, I proposed to study the combined effect of n-3 FA and mild CR (20% CR) in preventing age-associated musculoskeletal loss. I speculate that mild CR will have very minimal dietary restriction associated bone loss. The muscles and bones act as two parts of the same functional unit of the musculoskeletal system. To determine the beneficial effect of n-3 FA+ mild CR on muscle health during aging, I will perform dual energy absorptiometry (DXA) to determine muscle mass; analyze fiber types, fat content, iron content, antioxidant enzymes and oxidative damage levels of muscle to determine muscle quality; analyze mitochondrial functions by measuring reactive oxygen species and ATP production, membrane potential, respiratory rates, and electron transport complex activities to determine muscle activity; analyze grip strength and treadmill endurance capacity to determine muscle strength. I anticipate that n-3 FA+ mild CR will prevent aging related decline in muscle mass, quality and function by maintaining muscle fiber numbers with reduced fat and iron accumulation and redox balance, thereby maintaining proper mitochondrial functions to provide sufficient energy. To determine the beneficial effect of n-3 FA with/without mild CR on bone health during aging, I will perform DXA to determine bone mass; analyze bone porosity, pore size distribution and fractions of mobile and bound water by nuclear magnetic resonance (NMR) to determine bone quality; analyze bone formation and bone resorption activities to determine bone remodeling status; analyze material testing of femur and biomechanical tests of vertebrae to determine bone strength and toughness against bone fracture. I anticipate that bone quality of n-3 FA with/without mild CR animals will be maintained due to balanced activities of bone forming and resorbing cells leading to superior BMD, less bone porosity, and better bone bound water, thereby improving bone quality and strength and reducing bone fragility and associated fractures. Recently, human and animal studies were carried out using 10-30% CR and showed certain protective effects including muscle function improvement. However, mild CR is expected to provide benefits only at median lifespan but may not cause a maximal lifespan as of 40% CR. We observed extended survival of mice fed n-3 FA+40% CR. It is of interest if mild CR in the presence of n-3 FA can extend the life span similar to that of 40% CR. I will also determine whether n-3 FA+ mild CR mediated healthy aging and prolongation of life is associated with reduction of genes related to inflammation and oxidative stress. This proposal will establish the prophaylactic efficacy of n-3 FA and mild CR against age-associated musculoskeletal loss, thereby ensuring healthy aging and prolongation of lifespan. My immediate career goal is to gain sufficient additional skills and knowledge necessary to be an independent researcher in the field of aging and aging-associated musculoskeletal biology under the guidance of mentors and advisors and generate sufficient preliminary data to apply for independent R01 grants. My long term career goal is to establish myself as a productive, grant-funded, independent investigator through sustained basic and translational research in the area of aging. I would like to develop dietary prophylactic and therapeutic strategies to prevent/treat age-associated deterioration of musculoskeletal health. After successful animal study, my ultimate goal is to pursue clinical trials to establish these strategies to improve human health during aging. The key elements of my research career development plan are: (1) gain education/training on new technologies/advanced basic and clinical knowledge relevant to the field of aging by taking didactic courses and intensive mentoring interactions (2) acquire specific training in grant writing (3) generate sufficient preliminary data to support competitive R01 grant application (4) submit grant proposals (5) present my work at national and international conferences (6) publish peer-reviewed papers (7) attend conferences and journal clubs and (8) establish a strong network with prominent scientists in the field of my research. My institute provides an excellent venue that has a remarkable depth of expertise and resources that are highly supportive of my scientific project, as well as my career development plans. My overall career development will be monitored by an advisory committee consists of nationally and internationally reputed scientists in the field of inflammation, oxidative stress, muscle biology, bone biology and aging. PUBLIC HEALTH RELEVANCE: Aging is associated with progressive loss of musculoskeletal tissue mass, quality and function. Both n-3 fatty acids and calorie restriction improve muscle function and n-3 fatty acids improve bone mineral density due to their anti-inflammatory and anti-oxidative properties. Therefore, I hypothesize that n-3 fatty acids and mild calorie restriction (20% less than ad libitum without reduction in vitamins and minerals) will prevent age-associated decline in musculoskeletal tissue mass, quality and function, thereby ensuring healthy aging and prolonging lifespan.

DESCRIPTION (provided by applicant): Aging is associated with increased inflammation and oxidative stress leading to progressive decline in musculoskeletal tissue mass, quality and function which increases the risk of falls and fractures in the elderly. Both n-3 fatty acids (FA) and calorie restriction (CR) are anti-inflammatory and anti-oxidative. CR improves muscle mass, quality and function and n-3 FA improves bone mineral density (BMD) and muscle function and prevents bone loss. We observed increased hind leg lean mass in n-3 FA fed mice. However, 40% CR is associated with increased bone loss. Therefore, I proposed to study the combined effect of n-3 FA and mild CR (20% CR) in preventing age-associated musculoskeletal loss. I speculate that mild CR will have very minimal dietary restriction associated bone loss. The muscles and bones act as two parts of the same functional unit of the musculoskeletal system. To determine the beneficial effect of n-3 FA+ mild CR on muscle health during aging, I will perform dual energy absorptiometry (DXA) to determine muscle mass; analyze fiber types, fat content, iron content, antioxidant enzymes and oxidative damage levels of muscle to determine muscle quality; analyze mitochondrial functions by measuring reactive oxygen species and ATP production, membrane potential, respiratory rates, and electron transport complex activities to determine muscle activity; analyze grip strength and treadmill endurance capacity to determine muscle strength. I anticipate that n-3 FA+ mild CR will prevent aging related decline in muscle mass, quality and function by maintaining muscle fiber numbers with reduced fat and iron accumulation and redox balance, thereby maintaining proper mitochondrial functions to provide sufficient energy. To determine the beneficial effect of n-3 FA with/without mild CR on bone health during aging, I will perform DXA to determine bone mass; analyze bone porosity, pore size distribution and fractions of mobile and bound water by nuclear magnetic resonance (NMR) to determine bone quality; analyze bone formation and bone resorption activities to determine bone remodeling status; analyze material testing of femur and biomechanical tests of vertebrae to determine bone strength and toughness against bone fracture. I anticipate that bone quality of n-3 FA with/without mild CR animals will be maintained due to balanced activities of bone forming and resorbing cells leading to superior BMD, less bone porosity, and better bone bound water, thereby improving bone quality and strength and reducing bone fragility and associated fractures. Recently, human and animal studies were carried out using 10-30% CR and showed certain protective effects including muscle function improvement. However, mild CR is expected to provide benefits only at median lifespan but may not cause a maximal lifespan as of 40% CR. We observed extended survival of mice fed n-3 FA+40% CR. It is of interest if mild CR in the presence of n-3 FA can extend the life span similar to that of 40% CR. I will also determine whether n-3 FA+ mild CR mediated healthy aging and prolongation of life is associated with reduction of genes related to inflammation and oxidative stress. This proposal will establish the prophaylactic efficacy of n-3 FA and mild CR against age-associated musculoskeletal loss, thereby ensuring healthy aging and prolongation of lifespan. My immediate career goal is to gain sufficient additional skills and knowledge necessary to be an independent researcher in the field of aging and aging-associated musculoskeletal biology under the guidance of mentors and advisors and generate sufficient preliminary data to apply for independent R01 grants. My long term career goal is to establish myself as a productive, grant-funded, independent investigator through sustained basic and translational research in the area of aging. I would like to develop dietary prophylactic and therapeutic strategies to prevent/treat age-associated deterioration of musculoskeletal health. After successful animal study, my ultimate goal is to pursue clinical trials to establish these strategies to improve human health during aging. The key elements of my research career development plan are: (1) gain education/training on new technologies/advanced basic and clinical knowledge relevant to the field of aging by taking didactic courses and intensive mentoring interactions (2) acquire specific training in grant writing (3) generate sufficient preliminary data to support competitive R01 grant application (4) submit grant proposals (5) present my work at national and international conferences (6) publish peer-reviewed papers (7) attend conferences and journal clubs and (8) establish a strong network with prominent scientists in the field of my research. My institute provides an excellent venue that has a remarkable depth of expertise and resources that are highly supportive of my scientific project, as well as my career development plans. My overall career development will be monitored by an advisory committee consists of nationally and internationally reputed scientists in the field of inflammation, oxidative stress, muscle biology, bone biology and aging. PUBLIC HEALTH RELEVANCE: Aging is associated with progressive loss of musculoskeletal tissue mass, quality and function. Both n-3 fatty acids and calorie restriction improve muscle function and n-3 fatty acids improve bone mineral density due to their anti-inflammatory and anti-oxidative properties. Therefore, I hypothesize that n-3 fatty acids and mild calorie restriction (20% less than ad libitum without reduction in vitamins and minerals) will prevent age-associated decline in musculoskeletal tissue mass, quality and function, thereby ensuring healthy aging and prolonging lifespan.