Fang, JiansongGao, LiMa, HuiliWu, QihuiWu, TianWu, JunWang, QiCheng, Feixiong2017-12-062017Fang, Jiansong, Li Gao, Huili Ma, Qihui Wu, Tian Wu, Jun Wu, Qi Wang, and Feixiong Cheng. 2017. “Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.” Frontiers in Pharmacology 8 (1): 747. doi:10.3389/fphar.2017.00747. http://dx.doi.org/10.3389/fphar.2017.00747.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492885Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.en-USquantitative and systems pharmacologynatural productstarget identificationagingnetwork-basedJournal Article2017-12-0610.3389/fphar.2017.00747