Project Summary This PPG will test the hypothesis that a loss in the reserve of the lung epithelial proteostasis network is the cause of age-related lung frailty. This highly integrated effort brings together scientists with a broad spectrum of expertise focused on this hypothesis with a goal of understanding the function of the proteostasis networks in the lung during aging in the unchallenged and influenza A-infected lung. The long term goal of this project is to use our understanding of the changes in proteostasis that develop over the lifespan to prevent the development of lung frailty and improve lung reserve in our aging population. The Project and Core leaders will generate parallel datasets including novel proteostatic imaging data, proteomic analysis of proteostasis networks in the lung and muscle tissue, and careful physiologic phenotyping of the severity of lung and skeletal muscle injury. These data will fuel discoveries of the molecular underpinnings of proteostatic frailty in the aging lung, suggest novel pathways for therapy, and provide the research community with new tools to image and quantify the function of proteostatic networks in the lung. Resources to support these interactions will be achieved through the collaborative structure of the Program Projects and the Cores. The Administrative Core bear the primary responsibility for coordinating these interactions through five interrelated specifics aims. Specific Aim 1. To support communication between the Project Investigators, the Core Leaders, Collaborating investigators, the Internal and External Advisory Committees and the Institutional Cores. Specific Aim 2. To provide a structure for the sharing of materials and dissemination of information between the Project Investigators, Core Leaders and their Collaborators. Specific Aim 3. To provide financial and regulatory oversight to the Project and Core Leaders and coordinate their interactions with Institutional Core Services. Specific Aim 4. To disseminate the discoveries made by the program project investigators through publications, presentations and the sharing of reagents and techniques to other institution and other investigators. Specific Aim 5. To foster an environment of collaborative interdisciplinary research and mentoring of students, post-doctoral fellows and investigators. The members of the Administrative Core will promote a collaborative, synergistic and interdisciplinary research program to fuel discoveries in the proteostasis networks of the aging lung.