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

机译:色氨酸-犬尿氨酸代谢抑制剂可延长果蝇的寿命

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摘要

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.
机译:在动物和人体研究中,色氨酸(TRY)形成的犬尿氨酸(KYN)上调与衰老有关。 TRY-KYN代谢受TRY 2,3-二加氧酶2(TDO)和AT P结合盒(ABC)转运蛋白的活性影响,调节TRY对细胞内TDO的访问。我们研究了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)对野生果蝇果蝇(Oregon-R)寿命的影响。 aMT和5MT延长了平均寿命和最长寿命(分别为27%和43%,21%和23%)。目前的结果是首次观察到TRY-KYN代谢抑制剂延长了果蝇的寿命,并且与有关TDO和ABC缺陷型果蝇突变体的延长寿命的文献和先前的研究相一致。抑制TDO和ABC转运蛋白的活性可能为抗衰老干预提供新的目标。

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