Anti-aging benefits of Selegiline:
Selegiline (brand names Jumex, Deprenyl, Eldepryl) is a selective, irreversible inhibitor of monoamine oxidase-B . Monoamine oxidase is an enzyme that breaks down monoamine neurotransmitters found in the brain, such as serotonin and melatonin. There are two isoforms of monoamine oxidase, type A and B. Type A preferentially targets serotonin and adrenalin, whereas type B targets phenylethylamine and dopamine. A monoamine oxidase inhibitor therefore, inhibits the action of the enzyme and prevents the breakdown of neurotransmitters, increasing their concentrations. Due to deprenyl’s ability to block the degradation of dopamine it is primarily used to treat Parkinson’s disease, a disease which results from low levels of dopamine production .
Deprenyl is normally used for the treatment of the early stages of Parkinson’s disease and is then used as an adjunctive therapy beside levodopa as the disease progresses. Deprenyl is generally taken at doses of 10 mg/day for Parkinson’s patients because doses higher than that lead to a loss of the selectivity of monoamine oxidase-B inhibition . The benefits derived from taking deprenyl for Parkinson’s patients is a prolongation of time before motor function deteriorates to the point that the patient must start taking levodopa. One study found levodopa treatment was delayed by 9 months in patients taking deprenyl . Another study showed that patients treated with both deprenyl and levodopa versus levodopa alone experienced less tremors and required a lower dose of levodopa to compensate for an increase in disability .
Aside from deprenyl’s use in treating Parkinson’s disease, it has shown promise as an anti-aging drug. Studies have been conducted on the life-prolonging abilities of deprenyl in rats . The first study was conducted in male rats and found, on average, an increased life-span from 147 weeks in the control (saline treated group) to 198 weeks in the deprenyl treated group (0.25 mg/kg/injected, 3 times a week) . This represents about a 26% increase in overall life-span. A second study also showed an increased life-span in rats given deprenyl (0.25mg/kg/injected, 4 times a week) – by about 16% . A third study showed an increased life-span of rats of 15% at 18 months and if the rats survived to 24 months, the drug increased life-span by 34% . Deprenyl was administered 3 times a week at a dose of 0.5 mg/kg by injection. This suggests the drug is more effective in an older population. A fourth study found no effect upon longevity in rats (0.5 mg/kg/day given in the rat’s water supply)  and a fifth study found increased morality in rats given deprenyl (0.5 mg/kg/injected, 3 times a week). A study conducted in a different species, Syrian hamsters, interestingly showed increased life-span in female hamsters, but not in male ones . Female hamsters used as controls lived on average for 408 days, whereas deprenyl treated (0.05 mg/kg, given by food) female hamsters lived on average for 475 days, representing a 15% increased life-span. A final study administered deprenyl (1 mg/kg orally, once daily) to canines and found that although there was not an overall effect on longevity, examining only the elderly dogs (10-15 years old), they found 80% (12/15) of deprenyl dogs had survived to the end of the study versus only 39% (7/18) of dogs who received placebo . These results again suggest deprenyl’s anti-aging effects may be more effective in an elderly versus a younger population. The discrepancies of these studies could potentially be explained by the dose administered (especially to the rats), with low doses (0.25 or 0.5 mg/kg injected 3 times a week) being beneficial and higher doses (1.0 mg/kg injected 3 times a week) being detrimental .
There are only a handful of studies conducted on the effect of deprenyl on human longevity. These studies were done by examining Parkinson’s patients taking deprenyl. A meta-analysis, which pools together all of the available data from 5 individual long-term studies, found no difference in longevity between Parkinson’s patients taking deprenyl (14 deaths in 297 patients) versus patients not taking deprenyl (17 deaths in 292 patients) . It is interesting to note that the average age of patients taking deprenyl in this study was 63.4 years. Experimental evidence from animals suggests the life-prolonging effects of deprenyl are only apparent in older animals, so perhaps the patients in the above study were too young to receive any benefit. Another meta-analysis examined the effect of monoamine-oxidase B inhibitors in general (using 9 studies on deprenyl) on morality and again found no difference between the control and monoamine-oxidase B inhibitor treated Parkinson’s patients .
In conclusion, there is evidence from animal studies that deprenyl can increase life-span. This evidence however, is lacking in human studies. This could be due to the fact that the above studies have been restricted to younger Parkinson’s patients taking doses higher then recommended for anti-aging benefits (10 mg/day versus 1-5 mg/day). This drug should therefore be considered a candidate for anti-aging ability until a time when more studies are conducted to prove specifically its effect on increasing longevity in humans. The prophylactic administration of a synthetic enhancer substance deprenyl, during postdevelopmental life could significantly slow the age-related decay of behavioral performances, prolong life, and prevent the precipitation or delay the onset of Parkinson’s disease and Alzheimer’s disease (15).
1. Olanow CW, Myllyla VV, Sotaniemi KA, Larsen JP, Palhagen S, et al. (1998) Effect of selegiline on mortality in patients with Parkinson’s disease: a meta-analysis. Neurology 51: 825-830.
2. Fabbrini G, Abbruzzese G, Marconi S, Zappia M (2012) Selegiline: a reappraisal of its role in Parkinson disease. Clin Neuropharmacol 35: 134-140.
3. Parkinson Study G (1993) Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med 328: 176-183.
4. Larsen JP, Boas J, Erdal JE (1999) Does selegiline modify the progression of early Parkinson’s disease?
Results from a five-year study. The Norwegian-Danish Study Group. Eur J Neurol 6: 539-547.
5. Kitani K, Minami C, Yamamoto T, Kanai S, Ivy GO, et al. (2002) Pharmacological interventions in aging and age-associated disorders: potentials of propargylamines for human use. Ann N Y Acad Sci 959: 295-307.
6. Knoll J (1988) The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl.Mech Ageing Dev 46: 237-262.
7. Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on L-deprenyl prolongs life in agedmale rats. Life Sci 47: 415-420. 8. Kitani K, Kanai S, Sato Y, Ohta M, Ivy GO, et al. (1993) Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence. Life Sci 52: 281-288.
9. Bickford PC, Adams CE, Boyson SJ, Curella P, Gerhardt GA, et al. (1997) Long-term treatment of male F344 rats with deprenyl: assessment of effects on longevity, behavior, and brain function. Neurobiol Aging 18: 309-318.
10. Gallagher IM, Clow A, Glover V (1998) Long-term administration of (-)-deprenyl increases mortality in male Wistar rats. J Neural Transm Suppl 52: 315-320.
11. Stoll S, Hafner U, Kranzlin B, Muller WE (1997) Chronic treatment of Syrian hamsters with low-dose selegiline increases life span in females but not males. Neurobiol Aging 18: 205-211.
12. Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, et al. (1997) Treatment with L-deprenyl prolongs life in elderly dogs. Life Sci 61: 1037-1044.
13. Kitani K, Kanai S, Miyasaka K, Carrillo MC, Ivy GO (2006) The necessity of having a proper dose of (-)deprenyl (D) to prolong the life spans of rats explains discrepancies among different studies in the past. Ann N Y Acad Sci 1067: 375-382.
14. Macleod AD, Counsell CE, Ives N, Stowe R (2005) Monoamine oxidase B inhibitors for early Parkinson’s disease. Cochrane Database Syst Rev: CD004898.
15. Knoll J (2003) Enhancer regulation/endogenous and synthetic enhancer compounds: a neurochemical concept of the innate and acquired drives. Neurochem Res. 2003 Aug; 28(8):1275-97.