Closeout Bridging Administrative Supplement to R01AG049611

项目总结 这项行政补充资金是为了完成以下项目的研究活动而申请的 在授权期结束后，父R01授予。父级奖项已经遭遇了三次重大延误 我们在过去四年中遭受的灾难性事件减缓了学科招募的速度 以及完成计划的目标：1)2017年的一次医院火灾，导致3个月的延误；2)洪水 2017年哈维飓风，导致与赠款有关的活动再次出现重大延误，原因是 洪水对人员和研究对象的住房和交通造成的破坏 2017-2018年冬季招聘速度大幅放缓；3)2020年新冠肺炎大流行， 又造成了5个月的延误。总体而言，这三个毁灭性事件加在一起大约是一年 家长助学金学习活动延迟。在这三项活动中，我们节省了用品和 病人护理成本，但我们无法节省人员成本。此结束语连接了管理 补充金将使我们能够在家长助学金的免费延期年内完成计划中的研究 而不改变其范围。家长的资助目标是检查基础的基本机制 加速老年人的骨质疏松症，并确定干预的潜在目标。核心假设是， 根据我们的初步数据，一个全球性的、基本的急性或慢性加速的机制 骨质疏松症是骨骼肌氨基酸运输减少，从而降低肌肉蛋白质合成代谢， 并可通过激活哺乳动物/雷帕霉素复合体1的机械性靶点(MTORC1)来逆转 用非氨基酸刺激的信号，如运动。目的是：1)确定2型糖尿病对健康的影响 骨骼肌氨基酸转运对膳食氨基酸的敏感性。2)确定做空的效果- 术语卧床休息不活动取决于骨骼肌氨基酸运输对饮食氨基酸的敏感性。3) 测定耐力运动对大鼠氨基酸转运对膳食氨基酸敏感性的影响 运动不足和2型糖尿病所致的急、慢性加速性骨质疏松症。

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.