Drug identification for translational strategies
Convincing evidence linking Longevity-Associated Genes (LAGs) to longevity will serve as a foundation for the search for small molecule compounds that might mimic the effect of LAGs. By identifying small molecules based on therapeutic hypotheses relating molecular function to healthy aging, effective translational research strategies can be developed and pilot studies can be designed. These findings will be disseminated to the research community.
Candidate chemical interventions could either modulate the activity of the protein encoded by a LAG or could induce a gene expression pattern associated with healthy aging.
This component of the Longevity Genomics project will focus on the analysis and integration of existing community data related to drug-like small molecules with longevity promoting properties. The assembly of this Longevity Drug data set will be based on the following activities:
Below is an illustration demonstrating the linkage between small molecule bioactivity, structure and gene expression using non-supervised clustering. The three data types can be obtained from public databases including PubChem, PubChem Bioassay and GEO, respectively.
Here we analyze drug- and age-related genome-wide expression data from public microarray and RNA-Seq experiments. One of the main objective is the identification drug candidates modulating the expression of longevity genes and pathways. For this, we compare age-related expression signatures with those from drug treamtments. The age-related query signatures are from recent publications such as Peters et al. (2015) and Sood et al. (2015), while the drug-related reference signatures are from the Connectivity Map (CMAP) and LINCS projects (Lamb et al. (2006).