Estrogenic Effects on Aged Muscle

雌激素对衰老肌肉的影响

• 批准号: 8528442
• 负责人: DAWN A LOWE
• 金额: $ 10.88万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528442
• 关键词: Address; Affect; Age; Aging; Antioxidants; Applications Grants; Area; Award; Biological Aging; Collaborations; Complement; Data; Educational process of instructing; Elderly; Environment; Estradiol; Estrogen Receptors; Estrogens; Experimental Designs; Faculty; Female; Functional disorder; Genes; Genomics; Goals; Hormonal; Hormones; Independent Scientist Award; Knowledge; Laboratories; Link; Mediating; Methodology; Minnesota; Modeling; Mus; Muscle; Muscle Weakness; Muscle function; Muscular Dystrophies; Myosin ATPase; Ovarian; Ovarian hormone; Oxidative Stress; Physical activity; Play; Postdoctoral Fellow; Quality of life; Research; Research Personnel; Research Proposals; Rodent; Rodent Model; Role; Services; Skeletal Muscle; Skeletal Muscle Myosins; Solid; Testing; Time; Tissues; Training; Universities; Woman; Women' s Health; Work; age effect; age related; aged; base; career; functional loss; graduate student; improved; innovation; male; muscle aging; muscle strength; muscular structure; muscular system; oxidation; prevent; programs; public health relevance; senescence; undergraduate student; young adult

DESCRIPTION (provided by applicant): The immediate career goal of this candidate is to expedite the research being conducted in her recently- awarded R01 (AG AG031743). This research is focused on the interactive effects of aging and estradiol on skeletal muscle and myosin functions. The long-term career goals of this candidate are to elucidate the overall mechanisms underlying age- and hormone-related skeletal muscle functional losses and to utilize this knowledge to devise optimal strategies for preventing, reversing, or at least slowing the progression of muscle weakness that occurs with age. These goals will be facilitated by a K02 award as a result of the candidate being relieved of many teaching and service-related faculty responsibilities, thus allowing her to intensively focus on research. The environment for the candidate to be successful in attaining these goals is exceptional. Senior, well-established investigators involved with the Center on Aging, The Muscular Dystrophy Center, and the Powell Center for Women's Health provide a network of excellence at the University of Minnesota in areas of biological aging, muscle, and women's health issues, respectively. A K02 award will afford the candidate time to become more engaged in activities sponsored by these Centers which will complement and advance her research program. In addition, as this "new investigator" is building her research team, relief time provided by a K02 award will be utilized to enhance the training she can offer to post-doctoral fellows and graduate and undergraduate students in her laboratory, expand current and establish new collaborations, and submit additional grant applications. The overall objective of the research that will be conducted during this award is to determine hormone-mediated mechanisms that contribute to muscle strength loss in aged females. Strength losses in females are likely related to changes in ovarian hormones in addition to aging, but mechanistic effects of these hormones on skeletal muscle have not been elucidated. Thus, the first aim of the research is to determine the extent to which estradiol treatment improves myosin function and muscle strength in ovarian- failed, aged mice. The second aim is to show that estradiol is beneficial to myosin and muscle strength independent of physical activity. The third aim of the research is to test the hypothesis that the beneficial effects of estradiol on myosin and muscle function are mediated by estrogen receptors which regulate oxidative stress-related genes. At the conclusion of this K02 award, the candidate expects to have established her research team as the leader in the area of aging and hormonal effects on muscle structure and function and to have contributed significantly to our understanding of estradiol deficiency in age-related muscle weakness. PUBLIC HEALTH RELEVANCE: Aging and loss of estrogen result in muscle weakness that impacts the quality of life of older adults. The applicant will conduct research to determine how estradiol treatment can benefit estrogen-deficient females by improving muscle strength.

描述（由申请人提供）：该候选人的近期职业目标是加快她最近获得的R01（AG AG031743）中正在进行的研究。本研究的重点是衰老和雌二醇对骨骼肌和肌球蛋白功能的交互作用。这位候选人的长期职业目标是阐明年龄相关的骨骼肌功能丧失的总体机制，并利用这些知识制定预防，逆转或至少减缓随年龄增长而发生的肌肉无力进展的最佳策略。这些目标将由K02奖促进，因为候选人被免除了许多教学和服务相关的教师职责，从而使她能够集中精力进行研究。候选人成功实现这些目标的环境是特殊的。参与老龄化中心，肌肉营养不良中心和鲍威尔妇女健康中心的资深，成熟的研究人员分别在生物老化，肌肉和妇女健康问题领域在明尼苏达大学提供卓越的网络。K02奖将为候选人提供更多的时间来参与这些中心赞助的活动，这将补充和推进她的研究计划。此外，由于这位“新研究员”正在建立她的研究团队，K02奖提供的救济时间将用于加强她可以在实验室为博士后研究员和研究生及本科生提供的培训，扩大现有合作并建立新的合作，并提交额外的资助申请。该研究的总体目标是确定导致老年女性肌肉力量丧失的肌肉介导机制。女性的力量损失可能与卵巢激素的变化以及衰老有关，但这些激素对骨骼肌的机械作用尚未阐明。因此，本研究的第一个目的是确定雌二醇治疗在多大程度上改善卵巢衰竭的老年小鼠的肌球蛋白功能和肌肉力量。第二个目的是表明雌二醇对肌球蛋白和肌肉力量有益，而不依赖于体力活动。本研究的第三个目的是验证雌二醇对肌球蛋白和肌肉功能的有益作用是由调节氧化应激相关基因的雌激素受体介导的假设。在这个K02奖的结论，候选人希望已经建立了她的研究团队作为在衰老和激素对肌肉结构和功能的影响领域的领导者，并为我们的年龄相关的肌肉无力的雌二醇缺乏症的理解做出了重大贡献。 公共卫生相关性：衰老和雌激素的丧失导致肌肉无力，影响老年人的生活质量。申请人将进行研究，以确定雌二醇治疗如何通过改善肌肉力量使雌激素缺乏的女性受益。