Deprenyl - Anti-Aging Drug Proven Effective in Dogs

One thing I learned in the recent Matt Kaeberlein / Tim Ferriss podcast that was completely new to me, was the Deprenyl lifespan study in dogs. Very interesting… you have to wonder why this line of research, after these great results, seems to have fizzled out (didn’t continue to be researched) after it was first published 20+ years ago.

Dosing in the dog lifespan study was 1mg/kg, daily after being started in middle age.

The typical dosing for L-Deprenyl in humans is about 10mg/day. I wonder if the doctors in our forum have any experience with patients using this drug and have thoughts on whether 60mg/day (for a 60kg person) is potentially tolerable over months of continuous use?

Its off-patent and cheap. Given that we don’t even yet have lifespan data in dogs for rapamycin (and many people are using it) its surprising that people are not already using L-deprenyl for longevity. Has anyone here every tried it?

An added benefit is that the method of action seems that it might be far removed from the common pathways of longevity drugs; mTOR, APMK, IGF-1, etc. and so if that is the case, it should be workable as a combination drug with rapamycin. (interestingly, I see in the literature that acarbose is contra-indicated for use with deprenyl for some reason).

I can see one issue with MAO inhibitors like deprenyl is that it has significant dietary implications: MAOIs and diet: Is it necessary to restrict tyramine? - Mayo Clinic

Dosing and Side Effects: Selegiline (Oral Route) Proper Use - Mayo Clinic

To assess whether L-deprenyl treatment begun in later life might enhance canine longevity in a fashion similar to that documented in rodents we also examined survival in a subset of elderly dogs who were between the ages of 10 and 15 yrs at the start of tablet administration and who received tablets for at least 6 months. In this subset, dogs in the L-deprenyl group survived longer (p < 0.05) than dogs in the placebo group. Twelve of 15 (80%) dogs in the L-deprenyl group survived to the conclusion of the study, in contrast to only 7 of 18 (39%) of the dogs who received placebo (P=0.017). Furthermore, by the time the first L-deprenyl treated dog died on day 427, 5 placebo treated dogs had already succumbed, the first on day 295. Specifically with respect to dogs, the findings reported herein suggest daily oral administration of 1 mg/kg L-deprenyl prolongs life when begun in relatively healthy dogs 10-15 years of age and maintained for the duration of the individual’s life, but in any event for no less than six months.

Full Research paper PDF: Sci-Hub | Treatment with L-deprenyl prolongs life in elderly dogs | 10.1016/s0024-3205(97)00611-5

and:

Among many pharmaceuticals that have been tested for their effects on longevities of different animal rodents, deprenyl is unique in that its effects on longevity has been tested in at least four different animal species by independent research groups and that the effect has been postulated to be due to its effect of raising such antioxidant enzyme activities as superoxide dismutase (SOD) and catalase (CAT) in selective brain regions. Thus far, in all four species of animals examined (rats, mice, hamsters, and dogs), a positive effect was demonstrated, although the extent of its effect is quite variable. Our group has examined the effect on longevities in rats and mice and on antioxidant enzymes in rats, mice, and dogs.

Although deprenyl has been claimed to have several other effects, such as a radical scavenging effect and a neuroprotective effect, past reports on its effects on longevities and antioxidant defenses are compatible with the notion that the drug prolongs the life span of animals by reducing the oxidative damage to the brain dopaminergic system during aging.

Further, our studies on F-344 rats as well as a dog study by Ruehl et al. suggest that the drug may at least partially prolong the life span of animals by enhancing immune system function and preventing tumor development in animals.

Full Research Paper PDF: Sci-Hub | Assessing the Effects of Deprenyl on Longevity and Antioxidant Defenses in Different Animal Models | 10.1111/j.1749-6632.1998.tb09910.x

Full Research Paper PDF: Sci-Hub | [Advances in Pharmacology] Volume 42 || Therapeutic Actions of L-Deprenyl in Dogs: A Model of Human Brain Aging | 10.1016/s1054-3589(08)60753-x

Highlights:

  • L-deprenyl administration improved spatial memory in aged dogs.
  • The optimal dose or length of treatment time of l-deprenyl varied among individual dogs.

Full Research Paper PDF: Sci-Hub | The effects of L-deprenyl on spatial short term memory in young and aged dogs | 10.1016/0278-5846(96)00014-0

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Wow, never expected any of those 90s era nootropics to come back with solid aging evidence

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The following study suggests that in rats, Deprenyl may shorten lifespan if the dosage is too high.

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Dang! Now you have me chasing still another anti-aging supplement for old dogs. I do prefer old dog studies to old rat studies. :smile:

If the studies continue to look good, I will pay out of pocket for a prescription.

Indian laws make it harder to export any kind of prescription anti-depressant drugs than it is to export rapamycin.

I did manage to get some trazodone from India a while back to try it in my sleep stack. I went through several vendors before I found one that would export it. Jagdish, wouldn’t at the time. After I bought some, my Inbox was flooded with vendors from Indiamart offering to sell some to me.
If anyone tries to source it from India and is successful, please let us know.

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I use buy-pharma.md for meds other than rapamycin. They also have some pet meds.

After you order from there you take your order number and verify it by online chat. And they usually ship out quickly.

Deprenyl as an MAOI may have serious interactions with some other meds like antidepressants. Checking drug interactions is important.

Aside from trazodone, they also have Valdoxan (agomelatine) which some people use for sleep.

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According to Wikipedia it comes with a depression and suicide risk warning…doesn’t look like it would work in humans like it does in dogs as dogs can’t commit suicide

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Its used as an anti-depressant, and all anti-depressant medications have that warning I think.

I’d still stay away from it, it’s registered as an MAO-B inhibitor and apparently it also interacts with a whole host of other complexes including probably mtor, so it has a lot of side effects whereas rapamycin just interacts with mtorc1

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This is something I will not experiment with in high doses (or any dose). As an anti-depressant it works in low doses, and I don’t want to take a chance with messing up my brain chemicals with high doses (or any dose). And, even if you did try it would it be difficult to stop taking it afterwards? I don’t plan to take that chance. Do your research on this one.

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“According to Wikipedia it comes with a depression and suicide risk warning”

As does almost every anti-depressant on the market.

As I am old and have no particular obligations other than to live longer, I am willing to take more chances and be willing to be the “canary in the coal mine” so to speak.
I don’t recommend anything I am doing to anyone else, especially younger people.

To paraphrase Michael Lustgarten Ph.D:
Live forever or die trying.

Maybe Elon musk will be able to upload my brain before I die? :grin:

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“Maybe Elon musk will be able to upload my brain before I die?”

Well, you never know. Many people believe the Apocalypse and WW III are about to happen. So maybe all our efforts will be wasted.

Deprenyl was one of the first drugs I tried some years ago for anti-aging. I opted for the Emsam 6 mg patch for about a month. The only difference I noticed was that it shortened my sleep cycle. I stopped after that. I may try a lower dose pill in the morning instead.

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Just familiar with the nootropic applications that seem to wane away. Most physicians have been warned repeatedly about MOA inhibitors due to the multitude of interactions. Psychiatrists would be our best resource for its risk to benefit value.

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I hate contributing hear-say, without URLs backing up what I’m reporting!! :frowning: But…

I’ve been taking selgene/deprenyl for 10yr. Like my rapa experience no discernable benefits. But my blood work looks great and can work like a 40 yr old. LOL not scientific for sure.

The “father” of the deprenyl research (??) said he originally started on 5mg/day 2 days, then 3 off. Seems deprenyl has a dropping off of its benefits over time so need rest periods. Also like LDN benefits from a few weeks to a month off period. TBD… Then the last i heard from him (?? dont remember where, but a few yrs ago) he said personally he was taking 1mg / day continuously. This is a human body sized dose. mg/kg???

Now, like rapa, optimal dossing sched may have been updated??? But it would be my guess, that 10mg/day/no rest periods for a typical human would not be optimal, but saying its my guess.

I was wondering when deprenyl was going to surface in antiaging news. Also when LDN (low dose naltrexone)) has a role too. So much to piece together!

Best to all, curt

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I hate thinking about such scenarios!!! For many years I packed raw carrots in my bag lunch. Every month or so I would have a serous choking event with stuck carrot chunks. As my life flashed in front of my eyes, I kept thinking how stupid would it be to die from “health protocols”!!! :frowning: ;( :frowning:

Now my (on the war path with me) Functional medicine Dr figured out a trick to cut my kitchen sink nutrical mixes morning / night with a heavy metals challenge (DMSA)) pee collection test. DOH!!! into the red lead and murcury and I eat clean clean food. But have over years risked questionable chinese style herb powders… Like the carrots seems to be a net negative health tactic!! I’m just mad as hell. I can hear it now, my Dr’s gloating over being “right”. Well he’s right! ;( Now I’ve tossed all the questionable powders, will try a water based lead test on a mixup of the powders disolved in water + vinegar (to disolve metalic lead). An experiment.

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Dr Ward Dean of FL was pitching deprenyl. Dean really hasn’t been active with publishing, recent work. And any other orgs more recent human studies prob should be given preference. But here’s Deans advocation:

DEPRENYL- DOSAGES FOR LIFE EXTENSION PURPOSES

As stated previously, Professor Knoll is a man who ‘practises what he preaches’ and reportedly takes two 5mg Deprenyl tablets per week. We (Dean, Fowkes and Morgenthaler) recommend the following age adjusted titrated dosage schedule in our book, Smart Drugs 2.

Age. Dosage

30-35 1mg twice a week
35-40 1mg every other day
40-45 1mg every day
45-50 2mg every day
50-55 3mg every day
55-60 4mg every day
60-65 5mg every day
65-70 6mg every day
70-75 8mg every day
75-80 9mg every day
80 plus 10mg every day

Kitani and his colleagues (1996) found that the optimum dosage of Deprenyl, (which caused the greatest upregulation [increase] of antioxidant enzymes [SOD and CAT] in the brain in long-term studies) decreased by a factor of 5 (or 10). This was compared with the optimal dose in relatively short-term studies (3 weeks).

Unfortunately, by the time the results were calculated which showed the greater efficacy of reduced dosages of Deprenyl in long-term studies, Kitani’s group had already nearly completed another study using the much higher dose calculated from the short-term studies.

Contrary to the researcher’s expectations, the Deprenyl treated animals (given the high dose of Deprenyl based on the short-term studies), lived shorter lives than did the controls!

Kitani’s group is now repeating the study using the much lower Deprenyl dose that was determined to be most effective from the long-term studies.

Their work in progress appears to confirm that this lower dosage will result in life extension benefits for the Deprenyl treated animals.

Consequently, in view of the results of Kitani and colleagues, I recommend that my life extension patients consider the recommended dosages above as ‘starting dosages,’ and that they consider reducing their dosages somewhat after several months.

Kitani also concluded that ‘the proper choice of the dosage in long term experiments appears to be the key factor.’

DEPRENYL- RECOMMENDED FORMS

Deprenyl hydrochloride (Selegiline, Jumex etc) is the prescription form that is most widely prescribed by the orthodox physicians.

Liquid Deprenyl Citrate (LDC) is Selegiline, which is considered to be superior. This form is generally recognised as the most pure and potent form of Deprenyl available. It also allows precise titration for anti-aging purposes, as each ml drop in the bottle is equivalent to 1mg deprenyl citrate.

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I have been taking deprenyl on and off for a couple decades so I have studied it a lot. I currently take 7.5 mg am and noon. I have a SNP that up-regulates MAOa. I find taking a lot of dopamine agonists such as tyrosine and mucuna increase energy and motivation as well as mood. I got the deprenyl, an MAOb antagonist, prescription because I believed it would increase dopamine. It turns out it is much more complex.

“Taken together, our consistent findings across the two different approaches provide strong evidence that MAO-A, but not MAO-B, is engaged in DA degradation.”

" acute pharmacological inhibition of MAO-B by KDS2010 and selegiline did not affect either phasic or basal DA levels, which was inconsistent with the traditional belief."

“We recently reported that MAO-B-mediated tonic GABA inhibition in the SNpc (substancia nigra) is critical for DA neuronal dysfunction and parkinsonian motor symptoms in various animal models of PD… Our findings suggest that the therapeutic effect of MAO-B inhibitors could be attributed to blocking astrocytic GABA synthesis rather than to blocking DA degradation.”
https://www.nature.com/articles/s12276-021-00646-3

So it seems my overactive MAOa SNP is related to that apparent dopamine deficit that is improved by dopamine precursors. It also explains why the 15mg / day of MAOb antagonist selegline did not reduce the amount of dopamine precursors I need for good mood, motivation, and cognition. Serotonin agonists do not help.

Before I discovered how to use dopamine precursors, I took bupropion and it worked well. I think I will cut back on deprenyl, restart bupropion, and cut back on the 18g/ day of tyrosine I take.

Deprenyl does not lead the “Cheese effect” associated with Tyramine at moderate doses.

“The much-feared “cheese-effect” (which can, among others, induce hypertensive crises) is not to be expected under therapeutic doses. At most a minor amplification occurs in the sympathicomimetic effect of tyramine.”
https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.22334

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I believe Ward Dean still uses Deprenyl. The last time I looked, it was pretty cheap. It’s a small dose for life extension purposes.

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I’m familiar with selegiline. I just can’t take MAOIs. It would be possibly fatal in my case with dexmethylphenidate and other interactions.

From my understanding, rare hypertensive reactions have been reported with typical oral doses when in conjunction with tyramine intake. Beware - one cannot be certain that hypertensive crises would not happen even if one sticks to lower than 10 mg.

There are just too many issues (ie serotonin syndrome) that can mess up dosing for this drug such that it’s not on my radar. Frankly, the acarbose interaction isn’t even the biggest issue for me (similarly applies to metformin and canagliflozin etc) but it is indeed a significant issue with enough unknowns for me to avoid in my personal situation.

Just as an example, estradiol (in BC) can easily increase selegiline concentration by 20-fold:

No reason for me to chase selegiline for now, so I don’t closely follow as of right now. However, if Dr. Matt K or another group happens to find solid data in dogs, I’d probably revisit it. It’s got potential just limited data with too many issues.

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