Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 134, Issue 3-4, Pages 69-78Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2012.10.002
Keywords
Aging; C. elegans; Dimethyl formamide; Dimethyl sulfoxide; Lifespan
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Funding
- National Institutes of Health National Center for Research Resources
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Lifespan extension through pharmacological intervention may provide valuable tools to understanding the mechanisms of aging and could uncover new therapeutic approaches for the treatment of age-related disease. Although the nematode Caenorhabditis elegans is well known as a particularly suitable model for genetic manipulations, it has been recently used in a number of pharmacological studies searching for compounds with anti-aging activity. These compound screens are regularly performed in amphipathic solvents like dimethyl sulfoxide (DMSO), the solvent of choice for high-throughput drug screening experiments performed throughout the world. In this work, we report that exposing C. elegans to DMSO in liquid extends lifespan up to 20%. Interestingly, another popular amphipathic solvent, dimethyl formamide (DMF), produces a. robust 50% increase in lifespan. These compounds work through a mechanism independent of insulin-like signaling and dietary restriction (DR). Additionally, the mechanism does not involve an increased resistance to free radicals or heat shock suggesting that stress resistance does not play a major role in the lifespan extension elicited by these compounds. Interestingly, we found that DMSO and DMF are able to decrease the paralysis associated with amyloid-beta(3-42) aggregation, suggesting a role of protein homeostasis for the mechanism elicited by these molecules to increase lifespan. (c) 2013 Elsevier Ireland Ltd. All rights reserved.
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