Deprenyl (later known as selegiline) was developed by Professor Josef Knoll of Semmelweis University in Hungary in the 1950s. It was first used as an anti-depressant and was later used for the prevention and treatment of Alzheimer’s and (especially) Parkinson’s Disease. Deprenyl’s value initially was based on the belief only that it was a monoamine oxidase B (MAO-B) inhibitor. MAO-B is an enzyme that degrades the neurotransmitters dopamine, epinephrine, nor-epinephrine and serotonin in the brain. MAO-B levels rise with age (Fig. 1)1 and it was believed that this caused a decrease in these neuro-transmitters, which resulted in depression, Parkinsonism, and other neurodegenerative diseases. By selectively inhibiting MAO-B, deprenyl was theorized to maintain these neuro-transmitters at more youthful levels.
In 1983, Dr. Walter Birkmayer in Germany reported that Deprenyl, combined with L-dopa, not only improved the on-off phases and rigidity of Parkinson’s disease and reduced adverse reactions to L-dopa, but also prolonged the life expectancy of Parkinson’s patients!2 Birkmayer’s preliminary report was confirmed by ten-year long studies in nearly 1,000 Parkinson’s patients- who added deprenyl to their regimens after L-dopa had lost its efficacy.3-6 The L-dopa-plus-deprenyl-regimen significantly delayed the progression of Parkinson’s symptoms, and increased life expectancy compared to those on L-dopa alone.
Autopsies showed that deprenyl prevented or retarded the degeneration of striatal dopaminergic neurons in the brain (see Fig. 2). Scientists in the U.S.7 and Finland8 recommended that Deprenyl treatment be started as soon as the Parkinson’s diagnosis was made.
But it wasn’t just Parkinson’s patients that were living longer with deprenyl. In 1988, Knoll rocked the gerontological community with a study that showed a dramatic extension of maximum lifespan of rats treated with deprenyl (Fig. 3).9
Knoll and his colleagues treated 132 24-month-old male rats, (equivalent to 60-year-old humans) with injections of saline or deprenyl three times/week. The average lifespan of the saline-treated group was 147 weeks. The oldest rat in the saline group was 166 weeks old when it died. In contrast, the first rat to die in the deprenyl group lived 171 weeks, (five weeks after the last control rat died), and the longest-living deprenyl-treated rat died in its 226th week! The average lifespan of the deprenyl-treated group was 198 weeks–i.e., higher than the previously-estimated maximum lifespan of the rat (182 weeks). Knoll claimed that this was the first time that administration of a drug or nutrient resulted in extension of a species’ known maximum lifespan.10
In addition to these dramatic findings, the scientists evaluated sexual functioning in the rats, as a measure of their brain striatal function. Because of the normal age-related decay of sexual function, none of the 2-year-old animals displayed full-scale sexual activity. In the saline group, the last signs of sexual activity had completely vanished by the 33rd week of treatment. In contrast, deprenyl treatment restored full-scale sexual activity in 64 out of 66 rats!11 Inspired by Knoll’s groundbreaking lifespan studies with deprenyl, researchers around the world began trying to duplicate his results in a variety of species. Researchers at the University of Toronto in Canada gave injections of deprenyl (0.25 mg/kg) or saline every other day to male Fischer rats starting at 23 to 25 months of age. The deprenyl-treated animals showed a significant increase in both mean and maximum survival.12 Scientists from the Tokyo Metropolitan Institute of Gerontology reported their results with 70 male Fischer 344, (F-344) rats treated with injections of deprenyl or saline 3 times a week from the age of 18 months until they died. Although their results were not as dramatic as Knoll’s, the average lifespan of deprenyl-treated rats after 24 months was 34% greater than saline-treated controls, lending support to the growing awareness of deprenyl’s life-extending properties (Fig. 4).13, 14
In Germany, scientists treated 14 immunosuppressed mice- beginning at 2 ½ months of age, with half the group receiving deprenyl-laced food. The last mouse in the control group died at the age of 5 months (2.5 months after the study began). In contrast, the last mouse in the deprenyl group died at the age of 14.5 months–1 year after the beginning of the study, having lived nearly three times as long as the longest-living control mouse!15
Scientists at the Jackson Laboratory in Bar Harbor, Maine, conducted studies on 2 strains of mice, starting at mean ages of 26 and 18.5 weeks. In the study that began at 26 weeks, there was a 77-day increase in mean female lifespan, and an 84-day increase in mean male lifespan. For the mice that began treatment at 18.5 weeks of age, the mean longevities were increased only 59 days in females, and 56 days in males. Despite the inconsistencies, the authors concluded that since all studies found increased lifespans in deprenyl-treated mice, further research with deprenyl as a life-extending substance was justified.16
In 1997, a team from Mannheim, Germany, reported on deprenyl’s effect on the lifespan of Syrian Hamsters. At the age of 13 months, 36 pairs of hamsters were treated–half of which received 0.05 mg/kg deprenyl in their food. The scientists surprisingly found that deprenyl significantly increased life span in the females, but not in males (Fig. 5).17 This was especially significant as females of this species normally had a shorter lifespan than males.