Oxenkrug Gregory F, Navrotskaya Valeria, Voroboyva Lyudmila, Summergrad Paul
Psychiatry and Inflammation Program, Department of Psychiatry, Tufts University, Tufts Medical Center, Boston, MA USA.
Fly (Austin). 2011 Oct-Dec;5(4):307-9. doi: 10.4161/fly.5.4.18414. Epub 2011 Oct 1.
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.
在动物和人体研究中，色氨酸（TRY）向犬尿氨酸（KYN）转化的上调与衰老相关。TRY - KYN代谢受TRY 2,3-双加氧酶2（TDO）和ATP结合盒（ABC）转运蛋白活性的影响，ABC转运蛋白可调节TRY进入细胞内TDO。我们研究了TDO抑制剂α-甲基色氨酸（aMT）和ABC转运蛋白抑制剂5-甲基色氨酸（5MT）对野生型雌性果蝇（俄勒冈-R）寿命的影响。aMT和5MT延长了平均寿命和最长寿命（分别延长了27%和43%，以及21%和23%）。本研究结果首次观察到TRY - KYN代谢抑制剂可延长黑腹果蝇的寿命，这与关于TDO和ABC缺陷型雌性果蝇突变体寿命延长的文献及先前研究一致。抑制TDO和ABC转运蛋白活性可能为抗衰老和抗年龄相关性肌肉减少性肌病（AAMPD）干预提供新靶点。
