Interventiondeprenyl
Alternate NameSelegiline
OrganismRattus norvegicus
Aging PhenotypeLife-span extension
Allele TypeN/A
StrainFischer 344 (male)
DescriptionMale rats were injected subcutaneously with (-) deprenyl three times weekly, beginning at 18 months of age. This treatment resulted in a significant life-span extension (Kitani et al, 1993).
In a different study, treatment with deprenyl (0.5 mg/Kg) for up to 20 months significantly increased mortality in the male Wistar rat (Gallagher et al., 1998).
Similar treatments have been found to increase life-span in mice, dogs, and hamsters. However, it should also be noted there are a number of reports of failure of (-)deprenyl treatment to extend life-span and shortening of lifespan by (-)deprenyl treatment has also been reported (reviewed in Kitani et al., 2002).
Gene FunctionN/A
Other Phenotypes(-) deprenyl is a MAO B (monoamine oxidase) inhibitor (Knoll, 1980) with anti-apoptotic and neuroprotective effects (Tatton et al, 1994; Olanow, 1996; Paterson et al, 1997; Maruyama and Naoi, 1999). (-) deprenyl can induce increases in superoxide dismutase (SOD) and catalase (CAT) activities in certain regions of the brain (Carillo et al, 1992) and spleen (ThyagaRajan et al, 2000). (-)deprenyl also mobilizes several humoral factors, including neurotrophic factors, TNF-alpha, and several interleukins (Tang et al, 1998; Muller et al, 1996; ThyagaRajan et al, 1998). (-)deprenyl treatment causes a reduction in incidence of tumors with age (Kitani et al, 1993).
HomologsN/A
Primary ReferenceKitani, K., Kanai, S., Sato, Y., Ohta, M., Ivy, G. O., and Carrillo, M. C. (1993). Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence. Life Sci 52, 281-8. [Abstract]
Other ReferencesKnoll, J. (1988). The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl. Mech Ageing Dev 46, 237-62. [Abstract]
Milgram, N. W., Racine, R. J., Nellis, P., Mendonca, A., and Ivy, G. O. (1990). Maintenance on L-deprenyl prolongs life in aged male rats. Life Sci 47, 415-20. [Abstract]
Kitani, K., Minami, C., Isobe, K., Maehara, K., Kanai, S., Ivy, G. O., and Carrillo, M. C. (2002). Why (-)deprenyl prolongs survivals of experimental animals: Increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of vari [Abstract]
Archer, J. R., and Harrison, D. E. (1996). L-deprenyl treatment in aged mice slightly increases life spans, and greatly reduces fecundity by aged males. J Gerontol A Biol Sci Med Sci 51, B448-53. [Abstract]
Ruehl, W. W., Entriken, T. L., Muggenburg, B. A., Bruyette, D. S., Griffith, W. C., and Hahn, F. F. (1997). Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci 61, 1037-44. [Abstract]
Stoll, S., Hafner, U., Kranzlin, B., and Muller, W. E. (1997). Chronic treatment of Syrian hamsters with low-dose selegiline increases life span in females but not males. Neurobiol Aging 18, 205-11. [Abstract]
Ingram, D. K., Wiener, H. L., Chachich, M. E., Long, J. M., Hengemihle, J., and Gupta, M. (1993). Chronic treatment of aged mice with L-deprenyl produces marked striatal MAO-B inhibition but no beneficial effects on survival, motor performance, or nigral [Abstract]
Bickford, P. C., Adams, C. E., Boyson, S. J., Curella, P., Gerhardt, G. A., Heron, C., Ivy, G. O., Lin, A. M., Murphy, M. P., Poth, K., Wallace, D. R., Young, D. A., Zahniser, N. R., and Rose, G. M. (1997). Long-term treatment of male F344 rats with depre [Abstract]
Gallagher, I. M., Clow, A., and Glover, V. (1998). Long-term administration of (-)-deprenyl increases mortality in male Wistar rats. J Neural Transm Suppl 52, 315-20. [Abstract]
Knoll, J. (1980). Deprenyl (selegeline): the history of its development and pharmaceutical action. Acat Neurol Scand Suppl 95, 57-80.
Tatton, W. G., Ju, W. Y., Holland, D. P., Tai, C., and Kwan, M. (1994). (-)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis. J Neurochem 63, 1572-5. [Abstract]
Olanow, C. W. (1996). Deprenyl in the treatment of Parkinson's disease: clinical effects and speculations on mechanism of action. J Neural Transm Suppl 48, 75-84.
Paterson, I. A., Barber, A. J., Gelowitz, D. L., and Voll, C. (1997). (-)Deprenyl reduces delayed neuronal death of hippocampal pyramidal cells. Neurosci Biobehav Rev 21, 181-6. [Abstract]
Maruyama, W., and Naoi, M. (1999). Neuroprotection by (-)-deprenyl and related compounds. Mech Ageing Dev 111, 189-200. [Abstract]
Carrillo, M. C., Kitani, K., Kanai, S., Sato, Y., and Ivy, G. O. (1992). The ability of (-)deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective. Life Sci 50, 1985-92. [Abstract]
ThyagaRajan, S., Madden, K. S., Stevens, S. Y., and Felten, D. L. (2000). Restoration of splenic noradrenergic nerve fibers and immune reactivity in old F344 rats: a comparison between L-deprenyl and L- desmethyldeprenyl. Int J Immunopharmacol 22, 523-36. [Abstract]
ThyagaRajan, S., Madden, K. S., Kalvass, J. C., Dimitrova, S. S., Felten, S. Y., and Felten, D. L. (1998). L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of noradrenergic nerve fibers in the spleens of old F344 rats. J Ne [Abstract]
Tang, Y. P., Ma, Y. L., Chao, C. C., Chen, K. Y., and Lee, E. H. (1998). Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments. J Neurosci Res 53, 593-604. [Abstract]
Relevant Links
Keywordsdeprenyl, selegiline, selegeline, Rattus norvegicus, SOD, superoxide dismutase, CAT, catalase, oxidative stress, oxidative damage, radicals, cancer, tumor, spleen, immune, humoral