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

Mech Ageing Dev. 2013 Mar;134(3-4):69-78. doi: 10.1016/j.mad.2012.10.002. Epub 2013 Jan 11.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Animals
  • Body Size
  • Caenorhabditis elegans / growth & development*
  • Chemotaxis
  • Dimethyl Sulfoxide / pharmacology*
  • Dimethylformamide / pharmacology*
  • Free Radical Scavengers / pharmacology
  • Free Radicals
  • Green Fluorescent Proteins / metabolism
  • Heat-Shock Proteins / metabolism
  • Homeostasis
  • Insulin / metabolism
  • Longevity / drug effects*
  • Peptide Fragments / metabolism
  • Phenotype
  • Signal Transduction
  • Solvents / chemistry
  • Time Factors

Substances

  • Amyloid beta-Peptides
  • Free Radical Scavengers
  • Free Radicals
  • Heat-Shock Proteins
  • Insulin
  • Peptide Fragments
  • Solvents
  • amyloid beta-protein (3-42), pyroglutamyl(3)-
  • Green Fluorescent Proteins
  • Dimethylformamide
  • Dimethyl Sulfoxide