K. Fortney, E. Morgen, I. Jurisica

Calorie restriction (CR) extends lifespan in mammals and can delay the onset of age-related diseases, including cancer and diabetes. Drugs that target the same genes and pathways as CR may have enormous therapeutic potential. Recently, genome-scale data on the responses of human cell lines to over 1000 drug treatments have become available. Here we integrate these data with gene expression signatures of CR, biological pathway information, and protein-protein and drug-target interaction networks to generate a prioritized list of candidate CR mimetics.
We collect previously published gene expression signatures of CR and screen them against high-throughput drug-response data to obtain sets of drugs that mimic CR at the transcriptional level. We annotate these candidate CR mimetics with information from drug-target, pathway, and protein interaction databases, and use clustering methods to characterize them in terms of their chemical properties and the proteins, pathways, and diseases that they target. We also compare candidate drug modes of action with those of known lifespan-affecting drugs such as rapamycin. Finally, we apply our analyses to rank drugs in terms of their therapeutic promise.

Keywords (Optional): 
Calorie restriction