Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs

• Main Authors: Alex eZhavoronkov, Anton A. Buzdin, Andrey V Garazha, Nicolas eBorissoff, Alexey A Moskalev
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2014-03-01
• Series: Frontiers in Genetics
• Subjects: Transcriptomics; geroprotector; aging-supressive drug; validation of drugs; signalling pathway cloud
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fgene.2014.00049/full

The major challenges of aging research include absence of the comprehensive set of aging biomarkers, the time it takes to evaluate the effects of various interventions on longevity in humans and the difficulty extrapolating the results from model organisms to humans. To address these challenges we propose the in silico method for screening and ranking the possible geroprotectors followed by the high-throughput in vivo and in vitro validation. The proposed method evaluates the changes in the signaling pathway cloud constructed using the gene expression data and epigenetic profiles of young and old patients’ tissues. The possible interventions are selected and rated according to their ability to regulate age-related changes and minimize differences in the signaling pathway cloud. This flexible and scalable approach may be used to predict the efficacy of the many drugs that may extend human longevity before conducting pre-clinical work and expensive clinical trials.