Drug repurposing for aging research using model organisms
File(s)
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2017-10
Date Acceptance
2017-05-07
Citation
Aging Cell, 2017, 16 (5), pp.1006-1015
ISSN
1474-9718
Publisher
Wiley
Start Page
1006
End Page
1015
Journal / Book Title
Aging Cell
Volume
16
Issue
5
Copyright Statement
© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://doi.org/10.1111%2Facel.12626
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Geriatrics & Gerontology
aging
C. elegans
computational predictions
Drosophila
drug repurposing
lifespan
PROTEIN-LIGAND COMPLEXES
CAENORHABDITIS-ELEGANS
LIFE-SPAN
DATABASE
INHIBITION
CHEMISTRY
RESOURCE
ONTOLOGY
GENETICS
SEQUENCE
C. elegans
Drosophila
aging
computational predictions
drug repurposing
lifespan
Aging
Animals
Caenorhabditis elegans
Databases, Pharmaceutical
Drosophila melanogaster
Drug Repositioning
Drugs, Investigational
Gene Expression
Healthy Aging
High-Throughput Screening Assays
Humans
Mice
Mitogen-Activated Protein Kinase 14
Molecular Docking Simulation
Rats
Small Molecule Libraries
Structure-Activity Relationship
Animals
Humans
Mice
Rats
Drosophila melanogaster
Caenorhabditis elegans
Mitogen-Activated Protein Kinase 14
Drugs, Investigational
Gene Expression
Structure-Activity Relationship
Aging
Small Molecule Libraries
High-Throughput Screening Assays
Drug Repositioning
Databases, Pharmaceutical
Molecular Docking Simulation
Healthy Aging
06 Biological Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status
Published
Article Number
5
Date Publish Online
2017-06-16