Drug repurposing for aging research using model organisms.

Autor: Ziehm M; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.; Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Gower Street, London, WC1E 6BT, UK., Kaur S; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK., Ivanov DK; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK., Ballester PJ; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK., Marcus D; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK., Partridge L; Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, Gower Street, London, WC1E 6BT, UK.; Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany., Thornton JM; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), The Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2017 Oct; Vol. 16 (5), pp. 1006-1015. Date of Electronic Publication: 2017 Jun 16.
DOI: 10.1111/acel.12626
Abstrakt: Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila. Our approach combines information on genetic effects on aging, orthology relationships and sequence conservation, 3D protein structures, drug binding and bioavailability. Overall, we rank 743 different drug-like compounds for their likelihood to modulate aging. We provide various lines of evidence for the successful enrichment of our ranking for compounds modulating aging, despite sparse public data suitable for validation. The top ranked compounds are thus prime candidates for in vivo testing of their effects on lifespan in C. elegans or Drosophila. As such, these compounds are promising as research tools and ultimately a step towards identifying drugs for a healthier human aging.
(© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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