Estrogenic Effects on Aged Muscle

雌激素对衰老肌肉的影响

• 批准号: 8149862
• 负责人: DAWN A LOWE
• 金额: $ 10.67万
• 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/8149862
• 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; Students; Testing; Time; Tissues; Training; Universities; Woman; Women' s Health; Work; age effect; age related; aged; base; career; functional loss; improved; innovation; male; muscle aging; muscle strength; muscular structure; muscular system; oxidation; prevent; programs; public health relevance; senescence; 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。这项研究的重点是衰老和雌二醇对骨骼肌和肌球蛋白功能的相互作用。该候选人的长期职业目标是阐明与年龄和激素相关的骨骼肌功能丧失的总体机制，并利用这些知识来设计最佳策略来预防、逆转或至少减缓肌肉无力的进展。随着年龄的增长而发生。 K02 奖将有助于实现这些目标，因为候选人将免除许多与教学和服务相关的教员职责，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非常特殊。衰老中心、肌肉萎缩症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衰老、肌肉和妇女健康问题领域为明尼苏达大学提供了卓越的网络。 K02 奖项将为候选人提供更多时间参与这些中心赞助的活动，这将补充和推进她的研究项目。此外，由于这位“新研究员”正在组建她的研究团队，K02奖提供的救济时间将用于加强她可以为实验室的博士后研究员以及研究生和本科生提供的培训，扩大现有并建立新的合作，并提交额外的资助申请。该奖项期间将进行的研究的总体目标是确定导致老年女性肌肉力量丧失的激素介导机制。除了衰老之外，女性力量下降可能还与卵巢激素的变化有关，但这些激素对骨骼肌的机制尚未阐明。因此，该研究的首要目的是确定雌二醇治疗在多大程度上改善卵巢功能衰竭的老年小鼠的肌球蛋白功能和肌肉力量。第二个目的是证明雌二醇对肌球蛋白和肌肉力量有益，而与体力活动无关。该研究的第三个目的是检验以下假设：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。在获得 K02 奖时，候选人希望将她的研究团队打造为衰老和激素对肌肉结构和功能影响领域的领导者，并为我们对年龄相关性肌肉无力中雌二醇缺乏的理解做出重大贡献。 公共卫生相关性：衰老和雌激素流失会导致肌肉无力，从而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提高肌肉力量来使雌激素缺乏的女性受益。