Kitani Kenichi, Minami Chiyoko, Yamamoto Takako, Kanai Setsuko, Ivy Gwen O, Carrillo Maria-Cristina
National Institute for Longevity Sciences, Aichi 474-8522, Japan.
Ann N Y Acad Sci. 2002 Apr;959:295-307. doi: 10.1111/j.1749-6632.2002.tb02101.x.
Past studies including our own have confirmed that chronic administration of deprenyl can prolong life spans of at least four different animal species. Pretreatment with the drug for several weeks increases activities of superoxide dismutase (SOD) and catalase (CAT) in selective brain regions. An up-regulation of antioxidant enzyme activities can also be induced in organs such as the heart, kidney, spleen, and adrenal gland, and all are accompanied by an increase in mRNA levels for SODs in these organs. The effect of deprenyl on enzyme activities has a dose-effect relationship of a typical inverted U shape. A similar inverted U shape also has emerged for the drug's effect on survival of animals. An apparent parallelism observed between these two effects of the drug seems to support our contention that the up-regulation of antioxidant enzymes is at least partially responsible for the life-prolonging effect on animals. Further, when a clinically applied dose of the drug for patients with Parkinson's disease was given to monkeys, SOD and CAT activities were increased in striatum of these monkeys, which suggests potential for the drug's applicability to humans. The drug was also found to increase concentrations of cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the above rat organs. Together with past reports demonstrating that deprenyl increases natural killer (NK) cell functions and interferon-gamma, and prevents the occurrence of malignant tumors in rodents and dogs, the mobilization of these humoral factors may therefore be included as possible mechanisms of action of deprenyl for its diverse antiaging and life-prolonging effects. The potentials of propargylamines, (-)deprenyl in particular, for human use as antiaging drugs remain worthy of exploration in the future.
包括我们自己的研究在内，过去的研究已经证实，长期服用司来吉兰可以延长至少四种不同动物物种的寿命。用该药物预处理数周可增加选择性脑区中超氧化物歧化酶（SOD）和过氧化氢酶（CAT）的活性。抗氧化酶活性的上调也可在心脏、肾脏、脾脏和肾上腺等器官中诱导产生，并且所有这些器官中SOD的mRNA水平都会升高。司来吉兰对酶活性的影响具有典型的倒U形剂量效应关系。该药物对动物存活的影响也呈现出类似的倒U形。在药物的这两种作用之间观察到的明显平行关系似乎支持了我们的观点，即抗氧化酶的上调至少部分地是其对动物寿命延长作用的原因。此外，当给猴子服用临床上用于帕金森病患者的剂量时，这些猴子纹状体中的SOD和CAT活性增加，这表明该药物对人类具有潜在的适用性。还发现该药物可增加上述大鼠器官中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）等细胞因子的浓度。与过去的报告表明司来吉兰可增强自然杀伤（NK）细胞功能和干扰素-γ，并预防啮齿动物和狗发生恶性肿瘤一起，这些体液因子的动员可能因此被纳入司来吉兰多种抗衰老和延长寿命作用的可能作用机制中。炔丙胺类化合物，特别是（-）司来吉兰，作为抗衰老药物用于人类的潜力在未来仍值得探索。
