Dimethyl sulfoxide and dimethyl formamide increase lifespan of C. elegans in liquid

► DMSO and DMF increase lifespan of Caenorhabditis elegans in liquid. ► DMF produces a stronger effect on lifespan that DMSO. ► The mechanism is independent of insulin-like signaling and dietary restriction. ► The DMSO and DMF increase in lifespan is not related to stress resistance. ► DMSO and DMF...

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Bibliographic Details
Published in:Mechanisms of ageing and development 2013-03, Vol.134 (3-4), p.69-78
Main Authors: Frankowski, Harald, Alavez, Silvestre, Spilman, Patricia, Mark, Karla A., Nelson, Joel D., Mollahan, Pamela, Rao, Rammohan V., Chen, Sylvia F., Lithgow, Gordon J., Ellerby, H. Michael
Format: Article
Language:English
Subjects:
Aging
Amyloid beta-Peptides - metabolism
Animals
Body Size
C. elegans
Caenorhabditis elegans - growth & development
Chemotaxis
Dimethyl formamide
Dimethyl sulfoxide
Dimethyl Sulfoxide - pharmacology
Dimethylformamide - pharmacology
Free Radical Scavengers - pharmacology
Free Radicals
Green Fluorescent Proteins - metabolism
Heat-Shock Proteins - metabolism
Homeostasis
Insulin - metabolism
Lifespan
Longevity - drug effects
Peptide Fragments - metabolism
Phenotype
Signal Transduction
Solvents - chemistry
Time Factors
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Summary:► DMSO and DMF increase lifespan of Caenorhabditis elegans in liquid. ► DMF produces a stronger effect on lifespan that DMSO. ► The mechanism is independent of insulin-like signaling and dietary restriction. ► The DMSO and DMF increase in lifespan is not related to stress resistance. ► DMSO and DMF improve the paralysis elicited by protein aggregation. 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-β3–42 aggregation, suggesting a role of protein homeostasis for the mechanism elicited by these molecules to increase lifespan.
ISSN:0047-6374
1872-6216
DOI:10.1016/j.mad.2012.10.002