Jordens R G, Berry M D, Gillott C, Boulton A A
Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Canada.
Neurochem Res. 1999 Feb;24(2):227-33. doi: 10.1023/a:1022510004220.
(R)-Deprenyl, the archetypical monoamine oxidase-B inhibitor, has been shown to increase life-span in a number of species. Although many theories for this effect have been suggested, for example, an increase in superoxide dismutase (SOD) activity, the mechanism of action has yet to be elucidated. To investigate this phenomenon, we have examined the effects of (R)-deprenyl, and some aliphatic propargylamines, in an experimental aging model in Drosophila melanogaster. Both wild-type Oregon-R type flies, as well as a SOD knock-out mutant strain were used. Flies obtained from a series of paired mates were divided equally among treatment groups. In all studies, flies were treated for the duration of life following adult emergence. The aging model consists of substitution of sucrose with galactose in the regular food media of the flies. Initial experiments confirmed that such a substitution resulted in a significant (p < 0.01, Breslow test) reduction in mean and maximal life-span of flies, an effect not due to nutrient deprivation. Inclusion of (R)-deprenyl and the aliphatic propargylamines in the media, at average daily doses in the range 0.5-1 ng/fly/day, led to a significant increase in mean and maximal life-span of galactose-treated, but not control flies. This effect was seen in both wild-type and mutant flies.
(R)-司来吉兰,典型的单胺氧化酶-B抑制剂,已被证明可延长多种物种的寿命。尽管针对这种效应提出了许多理论,例如超氧化物歧化酶(SOD)活性的增加,但其作用机制尚未阐明。为了研究这一现象,我们在黑腹果蝇的实验性衰老模型中研究了(R)-司来吉兰和一些脂肪族炔丙胺的作用。使用了野生型俄勒冈-R型果蝇以及一种SOD基因敲除突变株。从一系列配对交配获得的果蝇被平均分配到各治疗组。在所有研究中,果蝇在成虫羽化后终生接受治疗。衰老模型包括在果蝇的常规食物培养基中用半乳糖替代蔗糖。初步实验证实,这种替代导致果蝇的平均寿命和最大寿命显著降低(p<0.01,Breslow检验),这种效应并非由于营养缺乏所致。在培养基中加入(R)-司来吉兰和脂肪族炔丙胺,平均日剂量在0.5-1纳克/果蝇/天范围内,导致经半乳糖处理的果蝇(而非对照果蝇)的平均寿命和最大寿命显著增加。在野生型和突变型果蝇中均观察到了这种效应。