Project 2: Modulating mitochondrial function to promote proteostasis in the aging lung

As we near the end of the fourth year, the PPG investigators have published a total of 66 publications supported by this award, which are included in Appendix A. The most relevant publications to this renewal are highlighted with the individual projects below. The PPG investigators identified the need to develop approaches that could be used to interrogate proteostasis over the lifespan both during homeostasis and in response to systemic stress. All of the investigators emphasized the importance of developing technologies that could be applied to samples obtained from both mice and humans. Building on Dr. Morimoto’s success in the use of transcriptomic analyses to examine changes in proteostasis in C. elegans and in the aging human brain, and Dr. Balch’s success with proteomics, we performed a transcriptomic (RNA-Seq) analysis of 24 tissues in mice during homeostasis and selected tissues including flow sorted cell alveolar type II cells, alveolar macrophages, muscle satellite cells and brain microglia over the lifespan and proteomic analysis of a subset. This project has led to several published manuscripts and others in preparation or review.