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Front Genet. 2014 Mar 3;5:49. doi: 10.3389/fgene.2014.00049. eCollection 2014.

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

Author information

1
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia ; First Oncology Research and Advisory Center Moscow, Russia ; The Biogerontology Research Foundation London, UK ; Department of Experimental and Molecular Medicine, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia.
2
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia ; First Oncology Research and Advisory Center Moscow, Russia ; Department of Experimental and Molecular Medicine, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology Moscow, Russia ; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences Moscow, Russia.
3
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia ; First Oncology Research and Advisory Center Moscow, Russia ; Burnasyan Federal Medical Biophysical Center Moscow, Russia.
4
Department of Biological and Medical Physics, Moscow Institute of Physics and Technology Dolgoprudny, Russia ; Department of Ecology, Syktyvkar State University Syktyvkar, Russia ; Laboratory of Molecular Radiobiology and Gerontology, Institute of Biology of Komi Science Center of Ural Branch of Russian Academy of Sciences Syktyvkar, Russia.

Abstract

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:

aging-suppressive drug; geroprotector; signaling pathway cloud; transcriptomics; validation of drugs

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