Influence of non-steroidal anti-inflammatory drugs on Drosophila melanogaster longevity

Oncotarget. 2015 Aug 14;6(23):19428-44. doi: 10.18632/oncotarget.5118.

Abstract

Most age-related diseases and aging itself are associated with chronic inflammation. Thus pharmacological inhibition of inflammatory processes may be effective antiaging strategy. In this study we demonstrated that treatment of Drosophila melanogaster with 10 non-steroidal anti-inflammatory drugs (NSAIDs: CAY10404, aspirin, APHS, SC-560, NS-398, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, licofelone) leads to extension of lifespan, delays age-dependent decline of locomotor activity and increases stress resistance. The effect of the lifespan increase was associated with decrease of fecundity. Depending on the concentration, NSAIDs demonstrated both anti- and pro-oxidant properties in Drosophila tissues. However, we failed to identify clear correlation between antioxidant properties of NSAIDs and their pro-longevity effects. The lifespan extending effects of APHS, SC-58125, valeroyl salicylate, trans-resveratrol, valdecoxib, and licofelone were more pronounced in males, valdecoxib and aspirin - in females. We demonstrated that lifespan extension effect of NSAIDs was abolished in flies with defective genes involved in Pkh2-ypk1-lem3-tat2 pathway.

Keywords: Drosophila; Geotarget; anti-inflammatory drugs; geroprotector; lifespan; longevity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases / genetics
  • 3-Phosphoinositide-Dependent Protein Kinases / metabolism
  • Amino Acid Transport Systems / genetics
  • Amino Acid Transport Systems / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Dose-Response Relationship, Drug
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Female
  • Fertility / drug effects
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 / metabolism
  • Lipid Peroxidation / drug effects
  • Longevity / drug effects*
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Motor Activity / drug effects
  • Oxidative Stress / drug effects
  • Sex Factors
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • Amino Acid Transport Systems
  • Anti-Inflammatory Agents, Non-Steroidal
  • Drosophila Proteins
  • Membrane Transport Proteins
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Glycogen Synthase Kinase 3