Key Points:
- A cumulative analysis of 15 L-deprenyl longevity studies, done over 27 years in six different countries, shows modestly significant lifespan extension effects in rodents.
- The drug appears most effective when administered at higher doses in older ages.
Showing that a therapeutic approach reproducibly extends lifespan across multiple mammalian species serves as a key attribute of any potential approach before entering human trials concerning longevity. The reproducibility of findings is a crucial cornerstone of the scientific method, and when several laboratories can replicate lifespan extension in different mammalian models, this provides strong evidence that the finding is biologically accurate and robust. In other words, reproducibility ensures lifespan extension findings in a specific laboratory are not due to that laboratory’s conditions, strain of animals used, or experimental procedure.
Now, as published in Ageing Research Reviews, Michael R. Bene from Johns Hopkins University in Baltimore, Maryland, presents a cumulative review of 15 studies that tested the effects of L-deprenyl on lifespan extension across multiple mammalian species. Interestingly, Dr. Bene found that the combined data across rodents, specifically, mice, rats, and hamsters, showed that L-deprenyl conferred a modestly significant extension of average lifespan. Furthermore, Dr. Bene reassessed data from a study using dogs and noted L-deprenyl conferred a non-significant trend toward lifespan extension. Interestingly, Dr. Bene also found that L-deprenyl’s impact on lifespan is dose- and age-dependent—a higher dose and beginning administration at later ages had greater effects. These findings may pave the way for future clinical trials testing whether L-deprenyl counteracts aging in humans.
Background Behind L-Deprenyl
L-deprenyl, also known by its generic name selegiline, is a prescription medication primarily used to treat symptoms of Parkinson’s disease in pill form and, in a transdermal patch form, major depressive disorder. Moreover, L-deprenyl has been explored for off-label uses in attention-deficit hyperactivity disorder (ADHD). Furthermore, L-deprenyl has shown potential neuroprotective effects in rodent studies, though whether it has the same effects in humans awaits clinical trial testing.
Key reasons behind Dr. Bene’s interest in L-deprenyl’s effects on lifespan in various mammalian species came from early studies, conducted in the 1980s, showing the drug could significantly extend lifespan in various animal models. Along these lines, initial promising results came from pioneering research from Joseph Knoll, reporting that L-deprenyl significantly prolonged the average life expectancy of male rats. Not only that, but in some cases, L-deprenyl nearly doubled the remaining lifespan of elderly male rats. Since then, similar average lifespan-extending effects have also been reported in mice, hamsters, and dogs.
A Johns Hopkins Researcher Mines Data from 15 L-Deprynyl Studies
In an attempt to get a better understanding of whether these reports of lifespan extension have merit, Dr. Bene cumulatively analyzed the data from 15 studies, where L-deprenyl’s effects on lifespan were tested in multiple mammalian species. Collectively, these studies were conducted over the course of 27 years, in six countries, in four species, using different dosages.
Intriguingly, in the mammalian rodent species, mice, rats, and hamsters, pooled data showed that L-deprenyl conferred a modest lifespan extension. The reproducibility of significant lifespan extension across multiple rodent species suggests that L-deprenyl actually confers a real effect on lifespan in rodents.
Dr. Bene also analyzed a study that reported modest lifespan extension in dogs. However, since there was such a large age variance between the dogs that entered the study, Dr. Bene used a statistical analysis to reassess L-deprenyl’s effects on dog lifespan, taking into account the age variance. While Dr. Bene’s calculations based on the study he analyzed did not show that L-deprenyl significantly extended dog lifespan, he did find a statistical trend toward lifespan extension. Thus, in addition to the positive findings with rodents, a trend toward lifespan extension in dogs adds further support to the view that L-deprenyl can extend lifespan across mammalian species.
Since different doses of L-deprenyl were used in the studies and because administration was started at varying ages across mammalian species, Dr. Bene ran a statistical analysis to see how these factors contribute to L-deprenyl’s effects on lifespan. Intriguingly, he found that using higher doses and beginning treatment at later ages were associated with greater effects on lifespan extension. These findings suggest that higher doses and starting L-deprenyl treatment in later life may have greater effects in counteracting aging.
“Carefully planned clinical trials will be required to determine if the findings presented in the current study hold relevance for L-deprenyl’s effects in humans,” said Dr. Bene in his publication.
Recommended L-Deprenyl Doses Range from 1.25 mg to 12 mg Daily
At recommended doses, ranging between 1.25 mg and 12 mg per day, taken orally, L-deprenyl is generally regarded as safe, with a manageable side effect profile. Such side effects are generally mild and may include nausea, dry mouth, stomach pain, dizziness, light-headedness, vivid dreams, low blood pressure upon standing, and irritation at the application site (the mouth if taken orally). Furthermore, taking excessive amounts of L-deprenyl, at significantly higher doses than recommended, can lead to life-threatening conditions with symptoms including a severe headache, hallucinations, a rapid pulse, and convulsions.
The doses most frequently used to extend lifespan across mammalian model species were roughly equivalent to 1.5 to 3 mg for the average human weighing about 155 pounds. Notably, while this is within the dosage range used in oral tablets for Parkinson’s disease symptoms, which is typically a 1.25 mg tablet taken daily, this dosage falls below that used in transdermal patches, which are typically 6 to 12 mg used daily. Thus, if the data supporting that a higher dose started at a later age confers the greatest effect on lifespan in animal models applies to humans, the transdermal patch may confer the best results.
Still, the optimal dosage of L-deprenyl will need to be addressed in clinical trials if, indeed, L-deprenyl is found to confer effects against aging in humans. Some research suggests that taking L-deprenyl at doses above 20 mg daily is safe and well-tolerated, which implies that the drug is safe at relatively high doses. In a similar vein, using too low a dose may not confer optimal aging intervention effects. Relatedly, determining the optimal age to take the drug will be necessary, since animal model studies suggest beginning treatment at a later age is better.
Additionally, according to Dr. Bene, to the best of his knowledge, the studies he examined constitute the largest body of evidence for a lifespan intervention in mammals, aside from two of the most well-known interventions: rapamycin and caloric restriction. Given the degree to which L-deprenyl has been shown to extend lifespan across mammalian species in Dr. Bene’s cumulative assessment of studies, it seems logical to begin clinical trials to determine whether the drug can counteract certain age-related conditions.
All the same, aside from research done in patients with Parkinson’s disease, a search of clinical trials shows only one study in another age-related disease, Alzheimer’s disease, completed without results posted. Other than that, there are no human trials underway testing L-deprenyl’s effects on aspects of aging. Perhaps future human trials could test L-deprenyl’s effects in other age-related neurological conditions, like mild cognitive impairment, since L-deprenyl has been shown to have neuroprotective properties in rodents. If such human trials demonstrate that L-deprenyl’s neuroprotective properties translate from rodents to humans, this could pave the way for other clinical trials testing whether the drug helps against other aspects of aging to possibly extend human lifespan.
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