1. Aging Cell. 2014 Apr;13(2):206-15. doi: 10.1111/acel.12163. Epub 2013 Nov 13.

A pharmacological network for lifespan extension in Caenorhabditis elegans.

Ye X(1), Linton JM, Schork NJ, Buck LB, Petrascheck M.

Author information: 
(1)Division of Basic Sciences, Fred Hutchison Cancer Research Center, Howard
Hughes Medical Institute, Seattle, WA, USA.

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.

© 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley
& Sons Ltd.

DOI: 10.1111/acel.12163 
PMCID: PMC3955372
PMID: 24134630  [Indexed for MEDLINE]