Closeout Bridging Administrative Supplement to R01AG049611

R01AG049611 的清仓桥接管理补充

• 批准号: 10281452
• 负责人: Elena Volpi
• 金额: $ 35.59万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10281452
• 关键词: Acceleration; Acute; Administrative Supplement; Adverse event; Aging; Amino Acid Transporter; Amino Acids; Anabolism; Award; Bed rest; Budgets; COVID-19 pandemic; Chronic; Clinical; Clinical Research; Complex; Data; Development; Direct Costs; Elderly; Equilibrium; Event; Exercise; FRAP1 gene; Fire - disasters; Floods; Funding; Grant; Health; Hospitalization; Hospitals; Housing; Human Resources; Hurricane; Inpatients; Intervention; Knowledge; Life; Mission; Muscle Proteins; Muscular Atrophy; Non-Insulin-Dependent Diabetes Mellitus; Parents; Patient Care; Physical Function; Protein Biosynthesis; Public Health; Reporting; Research; Research Activity; Research Project Grants; Research Subjects; Resistance; Sampling; Signal Transduction; Skeletal Muscle; Societies; Stimulus; Suspensions; Transportation; United States National Institutes of Health; Wages; Work; base; care costs; cost; dietary; disability; disability burden; experimental study; extracellular; improved; innovation; laboratory experiment; parent grant; prevent; recruit; resistance exercise; sarcopenia

PROJECT SUMMARY This administrative supplement for closeout bridge funding is requested to complete the research activities of the parent R01 grant after the end of the grant period. The parent award has suffered three major delays due to catastrophic events we have suffered over the past four years, which have slowed down subject recruitment and completion of the planned aims: 1) a hospital fire in 2017 which produced a 3 month delay; 2) flooding from Hurricane Harvey in 2017, which resulted in another major delay in grant-related activities due to destruction brought by the flood to personnel and research subjects' housing and transportation and dramatically reduced recruitment pace well into the Winter 2017-2018; 3) the COVID-19 Pandemic 2020, which caused another 5-month delay. Overall, these three devastating events add up to an approximately 1-year delay in parent grant study activities. During the three events we were able to save budget for supplies and patient care costs, but we were unable to save personnel costs. This closeout bridging administrative supplement will allow us to complete the planned studies during the no-cost extension year of the parent grant with no change to its scope. The parent grant objective is to examine the basic mechanisms that underlie accelerated sarcopenia in older adults and identify potential targets for interventions. The central hypothesis, based on our preliminary data, is that a global and fundamental mechanism of acute or chronic acceleration of sarcopenia is a reduction in skeletal muscle amino acid transport, which decreases muscle protein anabolism, and can be reversed by activation of the mammalian/mechanistic Target of Rapamycin Complex 1 (mTORC1) signaling with a non- amino acid stimulus such as exercise. The aims are: 1) Determine the effect of T2DM on the sensitivity of skeletal muscle amino acid transport to dietary amino acids. 2) Determine the effect of short- term bed rest inactivity on the sensitivity of skeletal muscle amino acid transport to dietary amino acids. 3) Determine the effect of resistance exercise on the sensitivity of amino acid transport to dietary amino acids in acute and chronic accelerated sarcopenia induced by inactivity and T2DM.

项目摘要 本行政补充收尾桥梁资金要求完成的研究活动， 在授权时段结束之后的父R 01授权。父母奖已经遭受了三次重大延误， 我们在过去四年中遭受的灾难性事件，这些事件减缓了受试者招募 并完成了计划目标：1）2017年的一场医院火灾，造成3个月的延误; 2）洪水 2017年哈维飓风导致赠款相关活动再次出现重大延误， 洪水对人员和研究对象的住房和交通造成的破坏， 2017-2018年冬季大幅降低招聘速度; 3）2020年COVID-19大流行， 又拖延了5个月。总的来说，这三次灾难性事件加起来大约需要1年的时间。 家长补助研究活动延迟。在这三个活动中，我们能够节省供应预算， 病人护理费用，但我们无法节省人力成本。这次收尾工作将行政 补助金将使我们能够在父母补助金的免费延长年度内完成计划中的研究 其范围没有变化。家长补助金的目标是研究基本机制， 加速老年人的肌肉减少症，并确定潜在的干预目标。中心假设， 根据我们的初步数据，急性或慢性加速的全球性和基本机制是否 肌肉减少症是骨骼肌氨基酸转运的减少，这降低了肌肉蛋白质的亲和力， 并且可以通过激活哺乳动物/雷帕霉素复合物1的机制靶（mTORC 1）来逆转 用非氨基酸刺激物如运动进行信号传导。目的是：1）确定T2 DM对 骨骼肌氨基酸转运对膳食氨基酸的敏感性。2)确定短- 长期卧床不活动对骨骼肌氨基酸转运对膳食氨基酸敏感性的影响。第三章 确定抗阻运动对氨基酸转运对膳食氨基酸的敏感性的影响， 由不活动和T2 DM引起的急性和慢性加速性肌肉减少症。