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. TR Y-KYN metabolism is affected by the activities of TR Y 2,3-dioxygenase 2 (TDO) and AT P-binding cassette (ABC) transporter regulating TR Y 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 TR YKYN metabolism, and in line with literature and previous studies on prolonged life span of TDO- and ABC-deficient female Drosophila mutants. Inhibitor of TDO and ABC transporter activity might offer the new target for anti-aging interventions.