Closeout Bridging Administrative Supplement to R01AG049611

项目总结

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.