Core A - Administrative and Systems Biology of Aging Core (ASBC)

CORE A: Administrative and Systems Biology Core – SUMMARY The Administrative and Systems Biology Core (ASBC, Core A), led by Drs. Nathan LeBrasseur and Sundeep Khosla who have a longstanding and productive history of collaboration, will provide the overall leadership as well as the infrastructure for the Program Project Grant (PPG). The three Projects defining mechanisms of cellular senescence in skeletal aging (Project 1), muscle aging (Project 2), and brain aging (Project 3) in the PPG represent independent but highly interactive proposals by experienced investigators who have a long track record of collaborative studies. A major goal of Core A, therefore, is to ensure optimal interaction and integration among the Projects. These interacting Projects also need the appropriate infrastructure and logistical support, such as sample acquisition and storage, data management, and central administrative coordination. In addition, as in the previous funding cycle, Core A will continue to provide statistical support to the investigators and trainees associated with the Projects and, where appropriate, the Cores. However, in keeping with the evolving bioinformatic needs of the Projects and also Core C (Drug Discovery and Development) and Core D (Senescence Molecular Phenotyping), we have enlisted a highly qualified expert in systems biology and bioinformatics, Dr. Hu Li, to (i) develop novel deep learning and systems biology platforms to uncover context- specific mechanisms of aging-driven senescence in bone, muscle, and brain; and (ii) to devise and leverage deep learning and systems-based single-cell analysis methods to decipher genes that modulate spatial coordination of cells in the aging microenvironment. Collectively, through the coordination, integration, and analysis of research activities and results across the three projects and four cores, Core A will ensure this PPG yields fundamental insights into the governing roles of p16 and p21 in cellular senescence and aging, critical data on the therapeutic potential of senotherapeutic compounds for age-related tissue dysfunction, and an advanced understanding and new hypotheses regarding cellular senescence as a mediator of inter-organ communication between bone, skeletal muscle, and brain.