title: Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan-kynurenine metabolism.
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.
authors: Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University, Tufts Medical Center, Boston, MA USA. goxenkrug@tuftsmedicalcenter.org
authors: Gregory F
authors: GF
authors: Oxenkrug
authors: Valeria
authors: V
authors: Navrotskaya
authors: Lyudmila
authors: L
authors: Voroboyva
authors: Paul
authors: P
authors: Summergrad
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007737:Kynurenine / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors*
chemical_list: C020774:alpha-methyltryptophan; C004182:5-methyltryptophan; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase