Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan-kynurenine metabolism
Extension of life span of Drosophila melanogaster by the inhibitors of tryptophan-kynurenine metabolism
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DOI：
10.4161/fly.5.4.18414
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发表时间：
2011-10-01
期刊：
影响因子：
1.2
通讯作者：
Summergrad, Paul
中科院分区：
文献类型：
--
作者：
Oxenkrug, Gregory;Navrotskaya, Valeriya;Summergrad, Paul
在动物和人类研究中，从色氨酸(Try)中上调犬尿氨酸(KYN)的形成与衰老有关。Try-kyn代谢受Try-2，3-双加氧酶2(TDO)和AT-P结合盒(ABC)转运体活性的影响，调节Try对细胞内TDO的访问。研究了TDO抑制剂α-甲基色氨酸(AMT)和ABC转运抑制剂5-甲基色氨酸(5MT)对野生品系雌性果蝇(Oregon-R)寿命的影响。AMT和5MT可延长小鼠的平均寿命和最高寿命(分别延长27%和43%，21%和23%)。本研究结果是首次观察到Try-kyn代谢抑制剂能延长果蝇寿命，这与tdo和abc基因缺陷的雌性果蝇突变体延长寿命的文献和前人的研究一致。抑制TDO和ABC转运蛋白的活性可能为抗衰老干预提供新的靶点。
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 AT P-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 interventions.