176 replies to this topic

[MikeDC]

About 30% people who tested NR say they don’t feel anything. It doesn’t mean it is not working. Almost all my coworkers are feeling improvement in energy and brain clearness. It works on everyone who are in the 50’s and older. It is prevention for people who are 30’s and 40’s. I am not advertising and I am telling you the truth. Eventually you will regret not taking NR sooner.

[normalizing]

so im not 50, but i do suffer from severe fatigue and lack of energy, thats why i started taking it, for months now, perhaps more than 3 months now with elevating the dose eventually. and as i said, ive noticed nothing! it didnt help fatigue at all. i figured i should try herbs and they kind of helped a bit more, at least it was noticeable unlike NR, but it didnt fix long term fatigue sadly. now ive stopped the NR, too expensive and crappy for me if it doesnt do its job which is to boost energy production. whats the point taking something that claims to boost energy, but doesnt?? and what kind of vicious thing to say is "oh just take it for years hoping when you are 50 you have more energy" this is like very nasty advertising.

[MikeDC]

so im not 50, but i do suffer from severe fatigue and lack of energy, thats why i started taking it, for months now, perhaps more than 3 months now with elevating the dose eventually. and as i said, ive noticed nothing! it didnt help fatigue at all. i figured i should try herbs and they kind of helped a bit more, at least it was noticeable unlike NR, but it didnt fix long term fatigue sadly. now ive stopped the NR, too expensive and crappy for me if it doesnt do its job which is to boost energy production. whats the point taking something that claims to boost energy, but doesnt?? and what kind of vicious thing to say is "oh just take it for years hoping when you are 50 you have more energy" this is like very nasty advertising.

If NR doesn’t fix your cronic fatigue, then your problem is not related to low NAD+.

[normalizing]

well, i cant figure it out thats all. i thought low NAD IS associated with lack of energy, no? but anyway, its still deception that people would recommend NR for when you lack energy. thats what this forum suggested when i complained about lack of energy, they advertised NR to help with that. and then also in the articles and news, it says NR is good for that too. so my conclusion is, be careful how you advertise this thing, its very irritating 

[MikeDC]

NR is good for chronic fatigue. But it doesn’t mean it will cure all chronic fatigues. Not all chronic fatigues are due to low NAD+.
Maybe you just need to do some exercise or some genetic issues not related to NAD+.

[YOLF]

 

so im not 50, but i do suffer from severe fatigue and lack of energy, thats why i started taking it, for months now, perhaps more than 3 months now with elevating the dose eventually. and as i said, ive noticed nothing! it didnt help fatigue at all. i figured i should try herbs and they kind of helped a bit more, at least it was noticeable unlike NR, but it didnt fix long term fatigue sadly. now ive stopped the NR, too expensive and crappy for me if it doesnt do its job which is to boost energy production. whats the point taking something that claims to boost energy, but doesnt?? and what kind of vicious thing to say is "oh just take it for years hoping when you are 50 you have more energy" this is like very nasty advertising.

If NR doesn’t fix your cronic fatigue, then your problem is not related to low NAD+.

 

 

 

well, i cant figure it out thats all. i thought low NAD IS associated with lack of energy, no? but anyway, its still deception that people would recommend NR for when you lack energy. thats what this forum suggested when i complained about lack of energy, they advertised NR to help with that. and then also in the articles and news, it says NR is good for that too. so my conclusion is, be careful how you advertise this thing, its very irritating 

 

 

NR is good for chronic fatigue. But it doesn’t mean it will cure all chronic fatigues. Not all chronic fatigues are due to low NAD+.
Maybe you just need to do some exercise or some genetic issues not related to NAD+.

This is exactly what I'm getting at. More types of pills swallowed = broader spectrum of benefits/treatment. So it's about finding as many ways possible of getting the results you want and seeing what works best. We're not supposed to diagnose ourselves with supplements (though our doctors can do it with drugs)... but the fact of the matter remains that it is possible to discover the details of your health, including pathologies, by benefiting from a bunch of things at once... then remove one, then another>>>> then try different combinations and use the studies to determine what mechanisms you are affecting and determine which of them will work best for your goals. You'll be surprised by what's possible despite all the naysaying and uninformed people... They aren't just uninformed though, they are just used to working within a scope where everything is measurable. A diagnostic and rescue method for every pill. Though you won't need a rescue method with supplements... rarely are any of them acutely dangerous unless you're very old and unhealthy to begin with.

 

For chronic fatigue, why not try some Alinia/Nitazoxanide from a foreign pharmacy? Also look into food intolerances and allergies. Stop eating, washing or otherwise using anything with a color in it that didn't come from food. Take the allergies to the next level and assess them according to the APG IV scale and remove foods from your diet which are molecularly related to your allergens... the test doesn't contain everything, but immunity against allergens evolves with time, the longer you have it, the more molecular relatives you'll find yourself allergic to. Getting a sleep study may also help, if you have environmental allergies, you will probably have sleep apnea and a filter sleep apnea machine will work wonders.

 

Supplement timing is also crucial, some things may not say so, but are best taken before bed. some work even better if you put them in enteric capsules... continued study will yield all sorts of great information.

 

 

[markmsb]

I've heard about trimethylglycine (Betaine) for helping with certaining aging related pathologies such as under methylation and inflammation. I always wondered why it hasn't been discussed more often outside of its workout benefits.

[sthira]

Any opinions Insilico's product -- "Longevity AI" -- it contains "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid."

"Insilico, a next-generation artificial intelligence company specializing in the application of deep learning proprietary technology for biomarker development and aging research, used pioneering high-performance computer simulations to probe of the effect of extracts on anti-aging pathways.

"The resulting formulation, called Longevity A.I, is an innovative combination of three natural nutrients that mimic known metabolic regulators of the same anti-aging pathways targeted by calorie restriction mimetics, which have long been associated with increased life expectancy.

"The active ingredients, Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid, shown by recent scientific studies to increase longevity, were identified from combinations of thousands of other candidates using deep-learning technology which calculated the precise formula for maximum activation of the anti-aging pathways."

[YOLF]

I've heard about trimethylglycine (Betaine) for helping with certaining aging related pathologies such as under methylation and inflammation. I always wondered why it hasn't been discussed more often outside of its workout benefits.

It's fallen out of favor, more methylation leads to more aging, esp where DNA methylation is concerned. I'll hypothesize that methylation of DNA determines not only the variety of functions specific to a cell, but for our purposes also the volume of functions. More methylation would therefore mean fewer functions to complete and accelerated maturity. When we're young and healthy, being much less methylated is okay because we are fit enough to accomplish these cellular tasks by the volume of stem cells... but as we get older, we need to cut corners in order to keep up with demand, so methylation is a sacrifice we make to do so. I regret all of the methyl donor supplements I've taken and I'm developing countermeasures for the damage/limitation they have very likely caused to my supplement regimen. But I'll get there, I've found lots of countermeasures.

 

The reason so many people did follow it was b/c early telomere research showed that more methylation slowed telomere attrition and made things like TA-65/Cycloastragenol, and Astragaloside IV more effective at a test specific marker. It was a way to ensure fantastic results, but in truth it has limited the performance of the telomere extending supplements in the cosmetic and youthful appearance department. As a result of trying to enhance performance metrics, we probably haven't seen quite what cycloastragenol could have been in terms of antiaging. So instead of slowly rejuvenating us, it mostly just made us age healthier. I'm about to expand my demethylation protocol, wish me life/luck!

Edited by YOLF, 31 October 2017 - 08:49 PM.

[YOLF]

Actually, I was just reading about thyroid hormones for someone, Thyroid hormone accelerates metabolism, and can be used to purge xenotoxins faster as a resutl, but it probably has the same effect on aging as cycloastragenol with methylation donors... Man I hope people realize that they're accelerating the visual aging of these poor autistic kids with these methyl donors... We definitely need to manage a way to reverse it.

[markmsb]

@ Yolf

 

I don't doubt that you've spent a lot of time and energy researching methylation, but I have seen nothing to the effect that methylation accelerates the aging process. I was under the impression that efficient methylation happens in younger people while in older people it becomes worse.

Edited by markmsb, 01 November 2017 - 06:33 PM.

[YOLF]

@ Yolf

 

I don't doubt that you've spent a lot of time and energy researching methylation, but I have seen nothing to the effect that methylation accelerates the aging process. I was under the impression that efficient methylation happens in younger people while in older people it becomes worse.

Is this DNA methylation that we're talking about or just molecular methylation? Methylation refers to a handful of different processes, of which, DNA methylation is distinct. Methylation produces catecholamines. I know that a deficit develops in that area from rampant MAO-B breaking down the products which signal processes in the liver.. Is it methylation in the liver which involves excretion of metabolic leftovers? Do we just lose neurometabolic and other metabolic functions which leads to a decline in methylation and the efficient movement of methyl donors throughout various systems. Hormones that improve skin quality have been found to demethylate certain areas of DNA.

 

I was taking TMG, methylfolate, and methylcobalamin together for a while. Prior to taking the stuff I was looking pretty young for my age, after several months I was back in the aging hole and looking about my age. I just don't see myself getting younger from taking methyl donors. It doesn't appear to help anything and there are no benefits of youthful vitality from it. Maybe wound healing at best. By genetics, I'm supposed to be pretty bad at making me feel better when I'm not taking them. I had undiagnosed health issues that left me a little anemic for B12 (methylcobalamin), and I'm glad I got that straightened out, but the benefits vanished after correcting the underlying problems.

 

Obesity and diabetes correlates with demyelination which requires methyl groups to function, but this has more do do I think with the burden placed on the liver to use that methyl for other things, thus starving the metabolism in the brain. Taking more methyl donors isn't the answer, demethylation of white fat to beige or brown however. I'm still of the mind that methylation needs to be a tightly controlled process where the methyl groups are coming from the right area of metabolism rather than from haphazardly taking it simply because markers have gone down. Instead, I think it is wiser to rejuvenate the processes that manage methylation and let youthful metabolism dictate methylation, which I might add is an ongoing process, so a spike in a water soluble vitamin might result in overloaded methylation and methylate where it is not needed. Shocking the affinities of the methylation system are likely to lead to harm. Proper metabolism requires a complex system that relies on ratios, proximity, molecular attraction, and more to determine the probability of creating the circumstances of youth. Bombing it with methyl donors is bound to be bad. The only time methylation is bound to be good is when it's blocking a gene for a disease, and as we are the survivors of the evolutionary process, we probably methylate/silence those areas of DNA by the healthy and efficient metabolism of other genetic activity which occur as a result of proper adaption to our environment.

 

That's where I stand, other explanations just look over complicated and end in conflict and hopefulness. Take the methyl donors and see if it makes you look younger or not. But what I think you'll find is that if you don't have homocystinuria, that you're methylating just fine and systemically improving hormone profiles will correct any slight methylation problems on it's own.

 

Also, here's my thoughts on cancers and methylation. Cancers are methylated in all the wrong places because they've maladapted (in a sustainable way) to the environment and are sustaining an atypical metabolic process that is interfering with the metabolism of the rest of the body.

 

I invite you to prove me wrong and show that haphazardly taking methyl donors is good in non disease states.

[markmsb]

Now that you cleared up your experiences and explained you thoughts in more detail as to why methyl donors could pose a problem in the aging process I understand better. Thanks for clearing that up an answering my question. 

[RWhigham]

Any opinions Insilico's product -- "Longevity AI" -- it contains "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid."

Withaferin A:

Ashwagandha root has about 0.1 % Withaferin A and ashwagandha leaves have about 0.5 % Withaferin A.

KSM-66®  spec ashwagandha root extract has Withanolides (%wt/wt) > 5%,  "Withaferin A" < 0.1%

Sensoril®  spec p41 ashwagandha root and leaf extract has Withanolide glycosides  ≥  10.0%,  "Withaferin A" ≤ 0.5%  100% leaf would approach 0.5%. They do not specify %leaf or %root. If we were to guess 50:50, "Withaferin A" in Sensoril® likely approaches 0.25%

 

125 mg per capsule of Sensoril® ashwagandha is 12 cents (Amazon - Dr's Best) and 300 mg per capsule of KSM-66® ashwagandha is 10 cents (Amazon - Jarrow).  300 mg/125 mg = 2.4x, so the "Withaferin A" content of either capsule is likely about the same

 

 

Gamma linolenic acid (GLA):  Borage seed oil - 24%   Borage oil borage leaves and flowers contain potentially toxic substances (pyrrolizidine alkaloids, of PAs) which could, in theory, cause harm if ingested over long enough periods of time. [The following shows PA seems to remain in the seeds, and is not present in the oil.]

 

 Toxicity: Borage seeds [also] contain small amounts of liver toxins called pyrrolizidine alkaloids (PA). However, testing has not demonstrated the presence of the alkaloid in the seed oil. Most commercially available borage seed oil is, therefore, likely to be PA-free and present no risk of PA toxicity. Measuring PA with a new fast technique showed it  was < limit of detection < 0.2 mcg/g.  Still, I would check my liver health periodically when using any herbal products.

 

Other sources (evening primrose oil & black cumin seed oil) contain much less GLA and these oils may not be equivalent. Evening Primrose oil which is much higher in alpha-linolenic acid than borage oil has a different sphere of application. Perhaps the same could be said for black cumin seed oil.

 

For rheumatoid arthritis the GLA dose is 1-3 g per day. Taking this much GLA from non-borage oils would likely include an undesirably large amount of other oils. 

 

Ginsenoside Rg3:

Red panax ginseng concentrate contains 0.44 % Table 4  assuming this table refers to % (likely lost in the translation from chinese). Good quality ginseng (old roots) is so expensive that I have never considered it.

 

Edited by RWhigham, 02 November 2017 - 01:00 AM.

[normalizing]

it seems withaferin a might also be toxic to humans in high doses, even if it is claimed to help protect against cancer. maybe its whole high toxicity is related to preventing cancer in that regard? but i would be cautious of consuming high amounts, as it seems to be the defense mechanism of the plant against predators. also, not sure if ginsenoside works in similar way, being a defense mechanism and toxic in high amounts.

[YOLF]

it seems withaferin a might also be toxic to humans in high doses, even if it is claimed to help protect against cancer. maybe its whole high toxicity is related to preventing cancer in that regard? but i would be cautious of consuming high amounts, as it seems to be the defense mechanism of the plant against predators. also, not sure if ginsenoside works in similar way, being a defense mechanism and toxic in high amounts.

How do the ashwaganda benefits compare to quercetin? I know it's a sort of minor energy booster and can increase libido at certain doses. The quercetin benefits are said to be from it's senolytic activity and ability to extend the half life of other antioxidants such as Vit C. Other things with similar action such as apigenin and luteolin iirc are said to be both p53 and HTERT activators depending on the circumstances. Taking too much quercetin can lead to zero sperm counts though.

 

This article seems to challenge everything I said so it is probably largely due to the doses taken which are left out of the details. However lots of links are provided to his references, so the details are readily available for the interested.

http://www.peaktesto..._Quercetin.aspx

[sthira]

Any opinions Insilico's product -- "Longevity AI" -- it contains "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid."

One thing that perks me is not so much the individual ingredients this presumed "AI" selected, but rather that it's selecting at all. If it is. I mean, if this is true. That is, we're looking at a future -- how soon that future, who knows -- in which we continue to slowly replace our own thinking with that of machine's algorithms. In the same way I've now gotten somewhat reliant on using my iPhone's GPS to lead me around in best routes of daily city traffic, or directions out into the woods, how soon will it be before we transition our thinking about increased health and longevity aspirations over to AI?

Frankly, I don't really care about "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid." What's interesting is that some algorithm presumably sifted through dozens or hundreds or thousands of compounds or whatever, and "it" decided upon these three. Is it correct? Who knows. But this type of transition -- from lesser intelligence to greater intelligence -- will continue to enhance our not just our meaty bio bodies, but hopefully in all areas of our lives and in society's. This makes me happy.

[YOLF]

 

Any opinions Insilico's product -- "Longevity AI" -- it contains "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid."

One thing that perks me is not so much the individual ingredients this presumed "AI" selected, but rather that it's selecting at all. If it is. I mean, if this is true. That is, we're looking at a future -- how soon that future, who knows -- in which we continue to slowly replace our own thinking with that of machine's algorithms. In the same way I've now gotten somewhat reliant on using my iPhone's GPS to lead me around in best routes of daily city traffic, or directions out into the woods, how soon will it be before we transition our thinking about increased health and longevity aspirations over to AI?

Frankly, I don't really care about "Withaferin A, Ginsenoside Rg3 and Gamma linolenic acid." What's interesting is that some algorithm presumably sifted through dozens or hundreds or thousands of compounds or whatever, and "it" decided upon these three. Is it correct? Who knows. But this type of transition -- from lesser intelligence to greater intelligence -- will continue to enhance our not just our meaty bio bodies, but hopefully in all areas of our lives and in society's. This makes me happy.

 

I guess it depends on how good exactly that the AI is. Does it recognize and distinguish between marketing? A study publication is a complicated document, often made for marketing purposes and the publishers will pick obscure metrics to prevent competition. I get alot of information looking into studies under a very suspicious lens. 

 

What exactly is this supplement for and what does it propose to do? What's the AI's plan to defeat aging? Whose books has it been reading? Does it go strictly by what the material says or does it advance the material that it is reading?

[RWhigham]

Is deprenyl a positive addition to a rapa,metformin, low dose aspirin, blood pressure medication protocol or is it counterproductive to the best of your understanding.

 

Dose and Timing of Deprenyl for life-extension

 

Deprenyl should not be taken while young:   Here is one of many studies showing that.  A study of L-deprenyl subcutaneous 0.25mg/kg 3 times weekly in male B6D2F1 mice started at 26 months of age resulted in an 84-day mean lifespan increase, but only increased mean lifespan 56 days if started at 18 months [ANNALS OF THE NEW YORK ACADEMY OF SCIENCES; Kitani,K; 1067:375-382 (2006)]. Can Deprenyl (Selegiline) Extend Human Lifespan?

 

Background

• At low doses the main effect of deprenyl is irreversible inhibition of MAO_B.  (Google "deprenyl mao b inhibitor" for 78,000 refs)
• In old age, MAO_B increases by 30-50% or more  ref
• Excess MAO_B in old age may accelerate aging by increasing ROS (hypothesis)
• Deprenyl single-dose pharmacodynamics is quite different from the repeated-dose pharmacodynamics. For example: The single dose elimination half-life is 2 hours, whereas  the half-life can extend to 10 hours with regularly repeated high doses. 
• For life-extension purposes, the dose will be relatively small and  single-dose pharmacodynamics is assumed.

Premise:

Most older people will benefit from lowering MAO_B back to youthful level

Data::

A 10 mg dose inhibited 88% of MAO_B in a young persons. Normalize young MAO_B to 100 units. Then 10 mg inhibited 88 units from a baseline of 100. Recovery to baseline took 2 weeks. How close to baseline is not known.. 3.1% 1.6% or 0.8% correspond to 5, 6, or 7 half-lives. Without more data, we will speculate that 2 weeks was 5 to 7 half-lives.

Goal:

To calculate a dose P and time interval T that makes MAO_B straddle a level L lower than some starting baseline M..

Hypotheses:

(1) It seems evident the probability of two molecules meeting is a function of the concentration of each. So the amount of depletion is proportional to the amount of MAO_B and the amount of deprenyl present.

 

(2) MAO_B is produced where there is a shortage. As the shortage is eliminated, the production decreases. We assume that MAO_B is replaced at a rate proportional to the remaining depletion resulting in an exponential recovery to which we can assign a half-life H..

 

Definitions:

 L = desired level for MAO_B (in normalized units)

 P = deprenyl dose (in mg)

 T = interval between doses (in hours)

 M = MAO_B baseline = 100 when young and healthy, 130 when older  (in normalized units)

 A = MAO_B a few hours after the dose (after the deprenyl has been used up)

 B = MAO_B immediately before next dose

 D = Drop in MAO_B caused by a dose

 H = half-life (in hrs) of the MAO_B recovery,  speculative value is 48 to 67 hours

 k = how many recovery half-lives in the interval T, (k)(H) = T

(n) indicates a subscript, for example A(n) = B(n) - D(n)

When n is large, A(n), B(n), D(n) converge to A, B, and D, Then MAO_B will oscillate between A and B and straddle L.

 

From the definitions,

1)  B will be the peak level

2)  A will be the trough level

3) (B+A)/2 will be the midpoint level L

4) (B-A) will be the distance between peak and trough

5) (B-A)/2 will be the excursions above and below L.

6) [(B-A)/(B+A)](100%) = the percentage excursion from L    From dividing the excursion 5) by the level 3)

 

From hypothesis (1)  - the drop D is proportional to the dose P and level B, A 10 mg dose gives an 88 unit drop from a level of 100 units.

•   D(n) = (88)(B(n)/100)(P/10mg)   (Eq 1) 
•   A(n) = B(n)-D(n)  by definition of A,  now replace D(n)  and factor out B(n)
•   A(n) = [1-(88/100)(P/10)]B(n)
•   Define  w = 1-(88/100)(P/10)     (Eq 2)
•   A(n) = wB(n) 
•   A = wB         (Eq 3)

7)  B+A = B(1+w)

8)  B-A = B(1-w)

9) [(B-A)/(B+A)](100%) = [(1-w)/(1+w)](100%) = percentage oscillation about L

   From 3)  (B+A)/2 = L   replace A with wB

   B(1+w) = 2L   solve for B

   B = 2L/(1+w)                            (Eq 4)

 

For P = 2.5 mg  w = 0.78  (1-w)= 0.22  (1+w)= 1.78 and (1-w)/(1+w)= 0.12 = percentage oscillation about L

For P = 5.0 mg  w = 0.56  (1-w)= 0.44  (1+w)= 1.56 and  (1-w)/(1+w)= 0.28 = percentage oscillation about L

 

The oscillation amplitude with 5 mg is undesirable. We will use 2.5 mg dose, with w = 0.78 and +/- oscillation of 12%.

 

From Hypothesis (2) - assuming MAO_B after a dose returns exponentially toward baseline with half life  H

•   MAO_B = M + (A-M)2^-t/H     (Eq 5)    from hypothesis (2)
•   At the end of the dosing interval MAO_B will have risen from A to B. Substitute MAO_B = B and t = T = kH 
•   B = M + (A-M)2^-k                Eq 5 at t = kH    solve for k
•  (B-M)2^k = (A-M)     by rearranging 
•  2^k = (M-A)/(M-B)    reversing the signs to have positive values (M-A) and (M-B)
•  k = ln[(M-A)/(M-B)]/ln(2)     (Eq 6) 

Procedure: calculate as follows

  Let P = 2.5 mg which makes w = 0.78

  Choose L and M. - For an older person M = 130.

  Calculate:

•   B = 2L/(1+w)    from Eq 4 
•   A = wB       from Eq 3
•   k = ln[(M-A)/(M-B)]/ln(2)   from Eq 6
•   T= (k)(half-life) = (k)(48 to 67 hrs)        

Example 1: An Older person

  Let P = 2.5 mg which makes w = 0.78

  Let M = 130 (for an older person)

  Choose L = 89 (because the numbers come out nice)

  B = 2L/1.78 = 178/1.78 = 100

  A = wB = (0.78)(100) = 78     MAO_B will oscillate between 78 and 100 with mid-point 89

  then  M-A = 52  M-B = 30 

  k = ln[(M-A)/(M-B)]/ln(2) = ln(52/30)/ln(2) = 0.79

  T = kH = (0.79)(48 to 67 hr) =  38 to 53 hr

  Result: take 2.5 mg every other day , or perhaps MWF and let the avg be a bit higher than 89

 

Example 2: A Younger person (ill advised, but let's see what happens)

  Let P = 2.5 mg which makes w = 0.78

  Let M = 100  (younger person)

  Choose L = 67

  B = 2L/1.78 = 134/1.78 = 75

  A = wB = (0.78)(75) = 59      MAO_B will oscillate between 59 and 75  (this may be too low and shorten lifespan)

  then M-A = 41 and M-B = 25

  k = ln[(M-A)/(M-B)]/ln(2) = ln(41/25)/ln(2) = 0.71

  T = kH = (0.71)(48 to 67 hrs) = 34 to 48 hrs

  Result: take 2.5 mg every other day, same as example 1

 

Edited by RWhigham, 19 November 2017 - 07:39 PM.

[normalizing]

interesting... "Excess MAO_B in old age may accelerate aging" among thousand other things. lets just concentrate on that one thing and profit from it

[RWhigham]

interesting... "Excess MAO_B in old age may accelerate aging" among thousand other things. lets just concentrate on that one thing and profit from it

You could say he "36 month" mice that lived 50 months with deprenyl treatment started at 28 months profited. ref  So it would seem MAO_B is rather important.

[poonja]

Jesus, i was very kind of you to put such an effort to respond to my query regarding Deprenyl.  As I am nearly 71 years old, I will begin implementing 2.5 mg every MWF and see if I can notice any reaction.  I will continue unless there are any unpleasant side effects.  Thank you again.

[RWhigham]

Jesus, i was very kind of you to put such an effort to respond to my query regarding Deprenyl.  As I am nearly 71 years old, I will begin implementing 2.5 mg every MWF and see if I can notice any reaction.  I will continue unless there are any unpleasant side effects.  Thank you again.I am also starting 2.5 mg MWF 

 Josh Mitteldorf is taking or has taken 2.5 mg MWF.  Scroll to the top to see his discussion of deprenyl .

 

The damaging effects of excess MAO_B are investigated here:  MAO-B elevation decreases parkin ’ s ability to efficiently clear damaged mitochondria: protective effects of rapamycin   These data suggest that MAO-B induction can interfere with mitochondrial quality control via losses in parkin activity that in turn impact on mitochondrial turnover. Rapamycin may be an effective means of counteracting the effects of lost parkin function by independently enhancing autophagic removal of damaged mitochondria. 

 

The article shows rapamycin can help ameliorate the bad effects of excess MAO_B, but without actually lowering the MAO_B.

So deprenyl may be a good addition to a rapamycin regimen..

Edited by RWhigham, 20 November 2017 - 04:28 PM.

[Nate-2004]

From what I can tell it doesn't seem anyone knows *WHY* MAO-B increases with age? Perhaps there is something upstream? What's Deprenyl's mechanism of action?

[Nuke]

 

Is deprenyl a positive addition to a rapa,metformin, low dose aspirin, blood pressure medication protocol or is it counterproductive to the best of your understanding.

 

Dose and Timing of Deprenyl for life-extension

 

Deprenyl should not be taken while young:   Here is one of many studies showing that.  A study of L-deprenyl subcutaneous 0.25mg/kg 3 times weekly in male B6D2F1 mice started at 26 months of age resulted in an 84-day mean lifespan increase, but only increased mean lifespan 56 days if started at 18 months [ANNALS OF THE NEW YORK ACADEMY OF SCIENCES; Kitani,K; 1067:375-382 (2006)]. Can Deprenyl (Selegiline) Extend Human Lifespan?

 

 

Starting age does not seem to be a factor. The study in the citation is not the right one, it should be https://www.ncbi.nlm.../pubmed/8914495 .Secondly, in that paper, the biggest difference between them is not their age, but the strain of mouse used. From the paper - "We performed two experiments, the first using B6D2F1 males and females, and the second using B6CBAF1 males and females. In the first, L-deprenyl injections were initiated at 26 months of age, and in the second, treatment began at 18.5 months of age" So we can't really make any deduction from that. If you look at Table1, last column , you will see that the last 10% of the B6CBAF1 did a little better than the B6D2F1.

 

Also, from the newest papers on Selegiline and BPAP, they started far earlier (10 weeks) and got pretty good results.

 

Most of selegiline's life extension may not be coming from it being a MAOI-B, but rather from its catecholaminergic activity enhancing properties. Its would seem that BPAP outperforms Selegiline, while not having MAO-B inhibiting effects.

 

All studies are attached.

 

Personally, the earlier I start, the better. Unfortunately mine is still in the mail.

 

As for why MAO-B increases with age, IIRC it has to do with getting more glial cells as you get older.

Attached Files

•  Longevity study with low doses of selegiline(-)-deprenyl and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine(BPAP).pdf   310.7KB   1 downloads
•  L-Deprenyl Treatment in Aged Mice Slightly Increases Life Spans, and Greatly Reduces Fecundity by Aged Males.pdf   779.89KB   0 downloads
•  A longevity study with enhancer substances (selegiline, BPAP) detected an unknown tumor-manifestation-suppressing regulation in rat brain.pdf   766.12KB   0 downloads

[YOLF]

From Wiki:

 

 

Effects of deficiency in humans[edit]

While people lacking the gene for MAO-A display mental retardation and behavioral abnormalities, people lacking the gene for MAO-B display no abnormalities except elevated phenethylamine levels in urine, raising the question of whether MAO-B is actually a necessary enzyme. Newer research indicates the importance of phenethylamine and other trace amines, which are now known to regulate catecholamine and serotonin neurotransmission through the same receptor as amphetamine, TAAR1.^[25][26]

The prophylactic use of MAO-B inhibitors to slow natural human aging in otherwise healthy individuals has been proposed, but remains a highly controversial topic.^[27][28]

 

[YOLF]

Also, do rats become more obese with age as humans of this point in history do? Is it a change in the function of adipose tissue where people are skinny? Obesity is not listed as a risk factor for Parkinson's.

[RWhigham]

  A longevity study with enhancer substances (selegiline, BPAP) detected an unknown tumor-manifestation-suppressing regulation in rat brain.pdf

In the above reference, deprenyl originator Knoll reports that very low doses of deprenyl extend lifespan by means of  a "catecholaminergic activity enhancer" effect  in the brain.  "Deprenyl exerts in rats in 0.001 mg/kg its ‘specific’ enhancer effect and in 0.1 mg/kg its ‘non-specific’ enhancer effect." He goes on to say "BPAP, devoid of MAO-B inhibitory effect, is at present the available most selective and potent synthetic tryptamine-derived enhancer substance". Rats treated with BPAP, or very low dose deprenyl, maintained there learning ability into old age,and lived longer.  This is an entirely separate effect from MAO_B inhibition.

 

So BPAP (or very-low-dose deprenyl) seems to protect neurons in the brain of rats when taken from a very young age. The HED (human equivalent dose) for 0.001 mg/kg is 11.6 ug for a 70 kg human (1/6 HEW conversion factor for rats). The rats were treated subcutaneously for accuracy.  Oral deprenyl is about 10% bioavailable (and most available when taken with food). To avoid depressing MAO_B, the deprenyl probably should not be taken at the " 0.1 mg/kg its ‘non-specific’ enhancer effect"" level. when young  BPAP which has no MAO-B effect would be preferable.

 

The fact remains that

• Deprenyl is a well known selective inhibitor of MAO_B   ref ref ref
• MAO_B increases with age (perhaps as glial cells replace dying neurons)
• Excess MAO_B is undesirable and likely increases the rate of aging
• At 70 yrs of age, it seems prudent to reduce MAO_B back to youthful levels
• If there is also a beneficial "catecholaminergic activity enhancer" effect protecting neurons then so much the better.
• The 2.5 mg MWF calculated previously is for oral dosing

Edited by RWhigham, 20 November 2017 - 09:10 PM.

[YOLF]

Gene Editing for $1550 plus some minor materials. If we don't need MAO-B at all, maybe we should just figure out how to knock it out.

[RWhigham]

Gene Editing for $1550 plus some minor materials. If we don't need MAO-B at all, maybe we should just figure out how to knock it out.

Low MAO_B is associated with  attention deficit disorder, novelty seeking, impulsive, risky, thrill-seeking behavior. One wouldn't want to inhibit it altogether, perhaps just "dial it down".a bit.  Ref  Ref

Edited by RWhigham, 20 November 2017 - 10:08 PM.