Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs
- 1Department of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia
- 2First Oncology Research and Advisory Center, Moscow, Russia
- 3The Biogerontology Research Foundation, London, UK
- 4Department of Experimental and Molecular Medicine, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
- 5Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
- 6Burnasyan Federal Medical Biophysical Center, Moscow, Russia
- 7Department of Ecology, Syktyvkar State University, Syktyvkar, Russia
- 8Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences, Syktyvkar, Russia
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 collection of activated or suppressed signaling pathways involved in aging and longevity, termed 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. While many algorithmic solutions to simulating the induction of the old into young metabolic profiles in silico are possible, this flexible and scalable approach may potentially be used to predict the efficacy of the many drugs that may extend human longevity before conducting pre-clinical work and expensive clinical trials.
Keywords: geroprotector, aging-suppressive drug, signaling pathway cloud, validation of drugs, transcriptomics
Citation: Zhavoronkov A, Buzdin AA, Garazha AV, Borissov NM and Moskalev AA (2014) Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs. Front. Genet. 5:49. doi: 10.3389/fgene.2014.00049
Received: 09 December 2013; Accepted: 16 February 2014;
Published online: 03 March 2014.
Edited by:Elena G. Pasyukova, Institute of Molecular Genetics of Russian Academy of Sciences, Russia
Reviewed by:Hao Mei, University of Mississippi Medical Center, USA
Taru Deva, Biosymfonix, Denmark
Douglas Gray, Ottawa Hospital Research Institute, Canada
Copyright © 2014 Zhavoronkov, Buzdin, Garazha, Borissov and Moskalev. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Alex Zhavoronkov, The Biogerontology Research Foundation, 4 Hill Street, London W1J 5NE, UK e-mail: firstname.lastname@example.org;
Alexey A. Moskalev, Komi Science Center of Russian Academy of Sciences, Institute of Biology, Kommunisticheskaja St. 28, Syktyvkar 167982, Russia e-mail: email@example.com