A pharmacological network for lifespan extension in Caenorhabditis elegans
Article first published online: 13 NOV 2013
© 2013 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.
Volume 13, Issue 2, pages 206–215, April 2014
How to Cite
Ye, X., Linton, J. M., Schork, N. J., Buck, L. B. and Petrascheck, M. (2014), A pharmacological network for lifespan extension in Caenorhabditis elegans. Aging Cell, 13: 206–215. doi: 10.1111/acel.12163
- Issue published online: 11 MAR 2014
- Article first published online: 13 NOV 2013
- Accepted manuscript online: 17 OCT 2013 10:41AM EST
- Manuscript Accepted: 3 SEP 2013
- Howard Hughes Medical Institute
- Ellison Medical Foundation
- National Institutes of Health. Grant Number: DP2 OD008398
- NIA Longevity Consortium. Grant Numbers: 2 U19 AG023122, 8UL1 TR000109
- NIH Office of Research Infrastructure Programs. Grant Number: P40 OD010440
- oxidative stress;
One goal of aging research is to find drugs that delay the onset of age-associated disease. Studies in invertebrates, particularly Caenorhabditis elegans, have uncovered numerous genes involved in aging, many conserved in mammals. However, which of these encode proteins suitable for drug targeting is unknown. To investigate this question, we screened a library of compounds with known mammalian pharmacology for compounds that increase C. elegans lifespan. We identified 60 compounds that increase longevity in C. elegans, 33 of which also increased resistance to oxidative stress. Many of these compounds are drugs approved for human use. Enhanced resistance to oxidative stress was associated primarily with compounds that target receptors for biogenic amines, such as dopamine or serotonin. A pharmacological network constructed with these data reveal that lifespan extension and increased stress resistance cluster together in a few pharmacological classes, most involved in intercellular signaling. These studies identify compounds that can now be explored for beneficial effects on aging in mammals, as well as tools that can be used to further investigate the mechanisms underlying aging in C. elegans.