Pharmacological interventions in aging and age-associated disorders: potentials of propargylamines for human use.
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.
Kitani
Kenichi
K
National Institute for Longevity Sciences, Aichi 474-8522, Japan. kitani@nils.go.jp
Minami
Chiyoko
C
Yamamoto
Takako
T
Kanai
Setsuko
S
Ivy
Gwen O
GO
Carrillo
Maria-Cristina
MC
D000375:Aging / Q000187:drug effects*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008017:Life Expectancy; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010293:Pargyline / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D011437:Propylamines / Q000737:chemistry / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D011437:Propylamines; C009054:propargylamine; D012642:Selegiline; D010293:Pargyline; D002374:Catalase; D013482:Superoxide Dismutase