title: Dimethyl sulfoxide and dimethyl formamide increase lifespan of C. elegans in liquid.
abstract: 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.
authors: The Buck Institute for Research on Aging, Novato, USA.
authors: Harald
authors: H
authors: Frankowski
authors: Silvestre
authors: S
authors: Alavez
authors: Patricia
authors: P
authors: Spilman
authors: Karla A
authors: KA
authors: Mark
authors: Joel D
authors: JD
authors: Nelson
authors: Pamela
authors: P
authors: Mollahan
authors: Rammohan V
authors: RV
authors: Rao
authors: Sylvia F
authors: SF
authors: Chen
authors: Gordon J
authors: GJ
authors: Lithgow
authors: H Michael
authors: HM
authors: Ellerby
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D049628:Body Size; D017173:Caenorhabditis elegans / Q000254:growth & development*; D002633:Chemotaxis; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004126:Dimethylformamide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D005609:Free Radicals; D006360:Heat-Shock Proteins; D007328:Insulin; D010446:Peptide Fragments; D012997:Solvents; C532271:amyloid beta-protein (3-42), pyroglutamyl(3)-; D049452:Green Fluorescent Proteins; D004126:Dimethylformamide; D004121:Dimethyl Sulfoxide