Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan-kynurenine metabolism

Fly (Austin). 2011 Oct-Dec;5(4):307-9. doi: 10.4161/fly.5.4.18414. Epub 2011 Oct 1.

Abstract

Upregulation of kynurenine (KYN) formation from tryptophan (TRY) was associated with aging in animal and human studies. TRY - KYN metabolism is affected by the activities of TRY 2,3-dioxygenase 2 (TDO) and ATP-binding cassette (ABC) transporter regulating TRY access to intracellular TDO. We studied the effects of TDO inhibitor, alpha-methyl tryptophan (aMT), and ABC transported inhibitor, 5-methyl tryptophan (5MT), on the life span of wild strain female Drosophila flies (Oregon-R). aMT and 5MT prolonged mean and maximum life span (by 27% and 43%, and 21% and 23%, resp.). The present results are the first observation of the extension of life span of Drosophila melanogaster by inhibitors of TRY - KYN metabolism, and in line with literature and previous studies on prolonged life span of TDO- and ABC-deficient female Drosophila mutants. Inhibition of TDO and ABC transporter activity might offer the new target for anti-aging and anti-AAMPD interventions.

MeSH terms

  • Animals
  • Drosophila melanogaster / drug effects*
  • Drosophila melanogaster / physiology
  • Female
  • Kynurenine / metabolism*
  • Longevity / drug effects*
  • Tryptophan / analogs & derivatives*
  • Tryptophan / metabolism*
  • Tryptophan / pharmacology
  • Tryptophan / physiology
  • Tryptophan Oxygenase / antagonists & inhibitors*

Substances

  • alpha-methyltryptophan
  • 5-methyltryptophan
  • Kynurenine
  • Tryptophan
  • Tryptophan Oxygenase