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How the world got lost on
the road to an anti-aging pill
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February 11, 2013: by Bill Sardi
Biotechnologist Dr. Bruce Bryan emails to say his grandmother, who lived to 109 years of age, in good health most of the way, because he gave her 5 milligrams of deprenyl every morning.
Deprenyl (selegiline) is a drug that was developed in the 1960s for its anti-depressant effects (it is a monoamine oxidase MAO enzyme inhibitor) and is now primarily prescribed for Parkinson’s disease sufferers (trade names Eldepryl, Emsam, Zelapar, Azilect). It is surprising to learn that deprenyl (selegiline) is a molecule similar to methamphetamine, an illicit street drug, but is not psycho-active nor does it create addiction.
In the mid-1990s animal experiments revealed deprenyl prolongs life, first demonstrated in rodents and then dogs. It also was discovered that Deprenyl not only inhibited MAO but it worked in the brain by increasing the activity of internal (endogenous) antioxidant enzymes catalase and superoxide dismutase (SOD). However, deprenyl doesn’t activate glutathione like resveratrol does.
It was even shown to improve “verbal memory” among Alzheimer’s patients over two decades ago.
Today’s promising anti-aging pills, the red wine molecule resveratrol (rez-vair-ah-trol) as an example, produce more news headlines than deprenyl and its cousins.
The question arises, why hasn’t the public warmed up to the idea of deprenyl as a longevity agent given such promising science?
It wasn’t till 2006 that researchers found that deprenyl activates a gene transcription factor called Nrf2 which then increases the activity of endogenous antioxidants SOD and catalase. A more recent study corroborates this earlier finding. But it was well known over 20 years ago that deprenyl activated these internal antioxidants, just the gene that controlled this was unknown at the time.
A recent report describes Nrf2 as a “guardian of the healthspan and gatekeeper of species longevity.” Here is what the report said:
“Nrf2 activate more than 200 genes that are crucial in the metabolism of drugs and toxins, protection against oxidative stress and inflammation, as well as playing an integral role in stability of proteins and in the removal of damaged proteins via proteasomal degradation or autophagy. Nrf2 interacts with other important cell regulators such as tumor suppressor protein 53 (p53) and nuclear factor-kappa beta (NF-κB) and through their combined interactions is the guardian of healthspan, protecting against many age-related diseases including cancer and neuro-degeneration. We hypothesize that this signaling pathway plays a critical role in the determination of species longevity and that this pathway may indeed be the master regulator of the aging process.”
The Nrf2 pathway is now considered a biological route to longevity. Again, why no current clamor for deprenyl? It is an FDA approved drug, though anti-aging would be an off-label product claim.
Maybe its cost has inhibited consumers from using this modern fountain of youth. Let’s check.
While Deprenyl requires a prescription and payment for a doctor’s office visit, it costs as little as 34-cents per 5-milligram tablet ($10.20/month) and it can be acquired online by savvy consumers from veterinary supply houses without an Rx for as little as 1.7-cents a pill (99-cents for 2-month supply!).
So what would be the correct dose of deprenyl to activate Nrf2?
The biological pathway towards healthy longevity certainly involves the Nrf2 gene pathway. Nrf2 is molecularly activated by low-dose biological stressors.
A low-dose toxin activates Nrf2 whereas high-dose negates the beneficial effect. This low-dose effect is known as hormesis. Nrf2 is described as the pathway for hormesis.
The classic low-dose effectiveness curve has been demonstrated for deprenyl in an animal study. Doses of 0.25 and 0.50 milligrams per kilogram of body weight (equivalent to 35 mg and 17.5 mg in a 70 kilogram/160-lb human) increased the lifespan of laboratory mice whereas 1.0 mg per kilogram of body weight (70 mg for a 70-kilogram/160-lb human) led to the earlier demise of these animals. The hormesis effect is clearly demonstrated in this experiment. Lower doses activate antioxidants in the brain, a higher dose is detrimental.
However, deprenyl was recently shown to activate enzymatic antioxidants in rodents at a much higher dose, the equivalent human dose of 140 mg per day on a body weight basis (based on 160-lb/70 kilogram weight).
But then again, there is Dr. Baker at the top of this report saying 5 mg worked for his grandmother. And the animal experiment cited above also suggests very low doses are effective.
There is one disturbing study conducted over a decade ago which showed that low-dose Deprenyl shortened the lifespan of laboratory rats. But the vast majority of the science is very positive.
Over 25 years ago Joseph Knoll advocated deprenyl: “to slow the aging of the brain, the decay of behavioral performance, prolong life, and prevent or delay the onset of age-related neuro-degenerative diseases such as Parkinson’s and Alzheimer’s via the prophylactic daily administration of 1 mg deprenyl.”
Regarding deprenyl’s beneficial effects upon the brain, one online source addresses deprenyl’s ability to maintain levels of the brain chemical dopamine. Here is how it is explained: ”
In younger people, dopamine levels remain fairly stable. However, even in healthy individuals, after about age 45 average dopamine levels in the brain start to decrease, by about 13% for each 10 years of life. On this basis, by approximately age 130 the dopamine content would decline to around 30% of normal – which is typically the level seen in patients with early Parkinson’s disease. (When the level has fallen to 10% of normal, death is likely to ensue.) Thus some neuroscientists have said that if we were to live long enough, everyone would ultimately suffer Parkinson’s disease symptoms. In healthy persons, if the rate of decline could be slowed even modestly (perhaps down to 10% per decade, instead of 13%), then a very significant life-extension would be possible. It is believed that this can be achieved by regular usage with deprenyl.”
One report said “a rapidly growing number of people are already trying to slow the aging of their brain by taking deprenyl as a prophylactic agent.” But where is the deprenyl fan club? Where is a leading physician or researcher who advocates this drug for longevity? Deprenyl is not even among the top-200 selling drugs today.
Word has it that dog food in Canada is being fortified with deprenyl. The inclusion of deprenyl in chow for older dogs has been mulled over for a number of years.
Over a decade ago researchers said: “It is reasonable to expect that a prophylactic low dose administration of a safe brain (acetycholine) activity enhancer during the post-developmental phase of life (childhood) will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson’s disease and Alzheimer’s disease.”
It is interesting to note that researchers compared anti-aging molecules in 2004 and described DHEA as an “unfounded” anti-aging agent, resveratrol as a molecule in its early stages of testing, and deprenyl as an anti-aging molecule “that has undergone successful testing.”
What about potential side effects? A 10-milligram dose did not produce any more side effects than an inactive placebo tablet.
In dogs there is a 5% incidence of unacceptable side effects (vomiting, diarrhea, appetite loss, itchy skin, tremors, drooling, listlessness, disorientation, diminished hearing, or restlessness.)
Commonly reported (but not frequent) side effects in humans are heartburn, upset stomach and nausea and insomnia and irritability. The latter over-stimulant effects are reported to be quelled by magnesium supplementation.
So will humans live longer if they begin taking low-dose deprenyl. There is an online report of a physician who took deprenyl along with other dietary supplements and lived 108 healthy years.
Because of the undesirable stimulant side effect of deprenyl, and because the red wine molecule resveratrol has been demonstrated to protect dopamine-producing cells in the brain, maybe resveratrol will gain traction as an anti-aging pill. But not enough people are taking deprenyl or resveratrol pills to produce a generation of centenarians, at least not yet. © 2013 Bill Sardi, ResveratrolNews.com