176 replies to this topic

[poonja]

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.

[YOLF]

 

Can you tell us more about how P450 affects the deprenyl?

 

The deprenyl dose in this mouse study was 10 mg/kg given intraperitoneally. This is likely much higher than needed for life extension purposes,

I read the Ben Best entry. It seemed to me that their might be a way to benefit from higher doses if one overcomes the metabolic byproducts such as by taking glutathione. What do you think?

 

I'll have to look into those other enzymes.

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.

I did read somewhere that it isn't to be taken with metformin. Not sure about the rest.

[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.

I wish I knew.  I'd like to add it, but I don't know how to judge a proper chronic dose. Perhaps subjective effects of MAO-B inhibition could be a guide? I believe Dr Joseph Knoll and a number of his confidants did take it without a problem.

 

Deprenyl reduces 2E1. If we reduce it more than necessary there may be an increased cancer risk. However, the mice on deprenyl did not die of tumors at 36 months like mice normally do. So cancer may be a bogus concern.

 

Cytochrome P450 pharmacogenetics and cancer

The polymorphic xenobiotic metabolizing CYP enzymes can be mainly divided into two classes:

 

Class I, composed of CYP1A1, CYP1A2, CYP2E1 and CYP3A4, which are well conserved, do not have important functional polymorphisms, and are active in the metabolism of precarcinogens and drugs.

 

CYP2E1 is responsible for the metabolism and activation of a large number of low-molecular-weight chemicals, solvents, cancer suspect agents and a few drugs (Table 2). Thus, CYP2E1 might be an important determinant of human susceptibility to toxicity and carcinogenicity of industrial and environmental chemicals. However, polymorphisms affecting CYP2E1 expression or activity have not been found, probably because of high conservation due to a critical role of the enzyme in gluconeogenesis during conditions of starvation. By contrast, induction of the enzyme by, for example, alcohol might provide a more important factor for interindividual susceptibility to cancer in reactions mediated by CYP2E1.

 

Class II, composed of CYP2B6, CYP2C9, CYP2C19 and CYP2D6, which are highly polymorphic and active in the metabolism of drugs, but not of precarcinogens.

Edited by RWhigham, 27 October 2017 - 08:05 PM.

[RWhigham]

It seems humans make about twice too much MAO-B in later life as neurons get replaced by glial cells. MAO-B makes destructive ROS metabolites which we want to minimize. Selegiline and Deprenyl are the same thing.

 

Clinical pharmacokinetics and pharmacodynamics of selegiline. An update. The elimination half-life of selegiline is about 1.5 hours.  Within 2 to 4 hours of an oral dose of selegiline 10 mg, 86% of the platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO-B activity to return to the baseline values.  Further details are behind a paywall.

 

For the above case a single 6 mg dose should initially inhibit about 50% of MAO-B in platelets. 6 mg repeated weekly should give an oscillation between -25% and -75% averaging -50%. I would suggest taking 2.5 mg (1/2 tablet) 3x per week (7.5 mg/week) corresponding to 64% inhibition with smaller oscillations. That's what Josh Mitteldorf is taking Josh Mitteldorf - Deprenyl: understudied, little-known anti-aging drug (he started taking it in the comments). He reports that he does not feel any effect other than a slight personality improvement. Your experience may vary.

 

Note: taking too much or starting it way too early in life will reduce any benefit.

At age 50-60, 2.5 mg 2x per week might be best.

At age 40-50  2,5 mg 1x per week might be best. It's largely guess work.

Edited by RWhigham, 28 October 2017 - 05:51 AM.

[APBT]

Clinical pharmacokinetics and pharmacodynamics of selegiline. An update. The elimination half-life of selegiline is about 1.5 hours.  Within 2 to 4 hours of an oral dose of selegiline 10 mg, 86% of the platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO-B activity to return to the baseline values.  Further details are behind a paywall.

FULL TEXT: 

Attached Files

•  Clinical Pharmacokinetics and Pharmacodynamics of Selegiline.pdf   1.09MB   7 downloads

[YOLF]

It seems humans make about twice too much MAO-B in later life as neurons get replaced by glial cells. MAO-B makes destructive ROS metabolites which we want to minimize. Selegiline and Deprenyl are the same thing.

 

Clinical pharmacokinetics and pharmacodynamics of selegiline. An update. The elimination half-life of selegiline is about 1.5 hours.  Within 2 to 4 hours of an oral dose of selegiline 10 mg, 86% of the platelet MAO-B activity was inhibited and it took almost 2 weeks for platelet MAO-B activity to return to the baseline values.  Further details are behind a paywall.

 

For the above case a single 6 mg dose should initially inhibit about 50% of MAO-B in platelets. 6 mg repeated weekly should give an oscillation between -25% and -75% averaging -50%. I would suggest taking 2.5 mg (1/2 tablet) 3x per week (7.5 mg/week) corresponding to 64% inhibition with smaller oscillations. That's what Josh Mitteldorf is taking Josh Mitteldorf - Deprenyl: understudied, little-known anti-aging drug (he started taking it in the comments). He reports that he does not feel any effect other than a slight personality improvement. Your experience may vary.

 

Note: taking too much or starting it way too early in life will reduce any benefit.

At age 50-60, 2.5 mg 2x per week might be best.

At age 40-50  2,5 mg 1x per week might be best. It's largely guess work.

I'm not sure there isn't a reason to start taking this in your twenties. Why does everyone always put the interventions so far into old age? Why don't we want to inhibit all of the MAOB that results from aging from it's earliest point? And why not just counteract the resultant ROS with glutathione or more common antioxidants? 

 

I've said it before and the idea of monotherapies, silver bullets/pills, and that kind of thing are over rated. We're missing out on opportunities to slow aging if we accept limits... life span and youthspan are supposedly limits... but we don't accept them do we? Of course not. Besides, isn't it cruel to wait for someone to get irreversibly sick before improving their health? Sure you're generations seem to have been largely abandoned in that respect and most non-aging diseases stem from obesity, which could be virtually eliminated by giving kids vyvanse or similar as soon as they get chubby, but industrialized nations seem to have given up on youthful fitness. It's probably one of the largest evils of our time... what you're falling prey to is just an extension of that same medical neglect. It's a very deep and serious problem that we need to do something about.

[Heisok]

"Sure you're generations seem to have been largely abandoned in that respect and most non-aging diseases stem from obesity, which could be virtually eliminated by giving kids vyvanse or similar as soon as they get chubby, but industrialized nations seem to have given up on youthful fitness. It's probably one of the largest evils of our time... what you're falling prey to is just an extension of that same medical neglect. It's a very deep and serious problem that we need to do something about."

 

Yolf,

 

I agree with much of what you say, but the portion which I quoted above is troubling. Giving kids a medication, or some sort of targeted nutrient for obesity would be medical negligence in my opinion. I will not quote the editor directly, because it was many years ago. They are with L.E.F. This was over 10 years ago, when LEF started developing more and more formulas for weight loss or blood sugar control. Such products like combinations which include Irvingia, and White Bean extract and others.

 

In essence, they expressed a strong concern. Were they using ingredients that block some of the problems with poor diet, and other unhealthy behaviors. Were they in fact only limiting things such as blood glucose spikes, yet as unhealthy behavior continued, underlying health issues could continue to develop.

Edited by Heisok, 28 October 2017 - 04:28 PM.

[Advocatus Diaboli]

Re: post #94. I calculate the range of oscillation for one 6mg pill per week as about -20% to -60%, not -25% to -75%.

I ask #94 poster to provide the reasoning behind the -25% to -75% range in order to compare with my results.

 

Here is my reasoning:

 

0.6 x 86% = 51.6% or about 50% (using poster #94's implicit assumptions). 

 

Taking one pill on day zero will result in 50% inhibition after a few hours.

 

After one week 25% remains inhibited (assuming linearity over the almost 2 week return to baseline), meaning 75% is not inhibited. Take another pill (6mg) and 50% of that 75% uninhibited is now inhibited, or 37.5% of baseline, for a peak of 62.5% (25%+37.5%) inhibited a few hours after that second pill is taken at the end of the first week. The range of oscillation at that point is -25 to -62.5

 

Continuing on with the calculation will show that at the end of week 5 the range of oscillation is -20.0195...% to -60.009...% which will be seen to be converging on the range of -20% to -60% if one continues the calculation through time.

[Nate-2004]

Does anyone know if methylene blue does something similar in terms of inhibition?

[RWhigham]

YOLF

I'm not sure there isn't a reason to start taking this in your twenties.

 

The idea is to keep MAO-B near youthful levels. I would not chose to lower it further without psychiatric consultation.

Edited by RWhigham, 29 October 2017 - 05:20 AM.

[MikeDC]

This new study shows that inhibiting MAO-B is not the mechanism of increasing Rat’s life span. It is related to a previously unknown trigger in rat’s brain to suppress tumor growth. Since rat’s mostly die from tumors while human die mostly from metabolic related diseases, the life extension effect may not translate to humans.

https://insights.ovi...line/7/00076800

For a drug/supplement to have life extension effects on humans, it should improve metabolic health such as increase insulin sensitivity, lower cholesterol, reduce inflammation, etc and with no side effects. Nicotinamide and Rapamycin just don’t fit this profile. Metformin does improve metabolic health, but it has side effects.

So currently, only NR offers a practical way to extend life in humans. Klotho is another one, but there is no commercial Klotho for sale. Gaba seems to be the short term solution.

Edited by MikeDC, 29 October 2017 - 02:10 PM.

[MikeDC]

I also read a study that Mao-B doesn’t start to increase until 60 year old.

[Nuke]

I have been researching Selegeline for a while now, and ordered some last week. On the one hand for anti-aging, but it's effect on cognition, mood and motivation looks promising too. Plan on starting at 1.25mg every day, or maybe every other day. Can titrate the dose from there.

 

For interest sake, It seems that Dr Knoll is still going at it, at age 92. https://www.ncbi.nlm...pubmed/28623006 While this is more focused on BPAP, it is compared with Selegiline. Use Scihub to grab the full study.

 

At 29, I also believe that the younger we start the better chance we have in the long run and Selegeline fits neatly. Btw all the other things I take is in my profile. Not many strange things except some peptides. 

[Heisok]

Thanks Nuke. Not many commenting on Intra-Nasal Insulin these days. It looks like you are still cycling it. Do you have an opinion about how it is helping you anti-aging wise, or short-term benefits?

Edited by Heisok, 29 October 2017 - 09:09 PM.

[YOLF]

"Sure you're generations seem to have been largely abandoned in that respect and most non-aging diseases stem from obesity, which could be virtually eliminated by giving kids vyvanse or similar as soon as they get chubby, but industrialized nations seem to have given up on youthful fitness. It's probably one of the largest evils of our time... what you're falling prey to is just an extension of that same medical neglect. It's a very deep and serious problem that we need to do something about."

 

Yolf,

 

I agree with much of what you say, but the portion which I quoted above is troubling. Giving kids a medication, or some sort of targeted nutrient for obesity would be medical negligence in my opinion. I will not quote the editor directly, because it was many years ago. They are with L.E.F. This was over 10 years ago, when LEF started developing more and more formulas for weight loss or blood sugar control. Such products like combinations which include Irvingia, and White Bean extract and others.

 

In essence, they expressed a strong concern. Were they using ingredients that block some of the problems with poor diet, and other unhealthy behaviors. Were they in fact only limiting things such as blood glucose spikes, yet as unhealthy behavior continued, underlying health issues could continue to develop.

Obesity shortens lifespan... safe, lifelong amphetamine use does not (even if overdoses might... those who take amphetamines as children do not develop a tendency for abuse). Just lowering blood sugar is useless, it takes a pound of cure for what could have been an ounce of prevention. Once the fat is there, it's mind control (signals brain to eat and make more fat), letting it form is like like letting a parasite or brainslug take over.

 

If you have to lower blood sugar, it's because you've become a diabetic or prediabetic and lowering blood sugar once you're fat rarely means you're going to lose weight. So with that methodology, you'll just be a fat person that has to keep taking pills instead of a skinny one that has to periodically take pills until whatever started making them fat passes or they learn better behaviors.

 

If you stop yourself from getting fat altogether, you'd never get as fat (morbidly obese) as has become common. The enjoyment that comes from being fat is also no different than drug use at the point where you have to eat so much that you're releasing epic, druglike quantities of serotonin. Food is just a drug that you can't live without.

 

If you were fat, what would you have wished you had been given medication? Forget diet pills, your doctor probably won't recommend them and they don't work nearly as well as medications. I've tried them all and amphetamines had the fewest side effects... diet pills will sap your motivation and destroy your reward system by creating artificially induced, long lasting satiation "highs" where you don't have to do anything to be satisfied and eventually start feeling satisfied with being fat. When you come off of diet supplements your head goes spinning and a sudden emptiness and unsatiated feeling returns and so does the behavior b/c the brain never got weaned of food high. If you were to get lipo, the window of time in which you are able to regress from abstaining from binge/overeating is much shorter, meaning you are less likely to fail and more likely to learn better self control,

[YOLF]

 

YOLF

I'm not sure there isn't a reason to start taking this in your twenties.

 

The idea is to keep MAO-B near youthful levels. I would not chose to lower it further without psychiatric consultation.

 

What's your definition of youthful? Youthful to me ends around 25, maybe earlier if we consider that aging cascades get kicked off in our late teens. I doubt we will be able to reach sustainable health and stop aging altogether unless we get our parameters young enough. How one feels about how old they look is also very important. I definitely won't feel as though I've reached the end of this endeavor until I look, feel, and perform 21 or better without swallowing pills. 

 

As for the usual age reversal concerns, I've already turned the clock back somewhat and I've only gotten wiser for it, there's nothing to lose except wrinkles

[YOLF]

This new study shows that inhibiting MAO-B is not the mechanism of increasing Rat’s life span. It is related to a previously unknown trigger in rat’s brain to suppress tumor growth. Since rat’s mostly die from tumors while human die mostly from metabolic related diseases, the life extension effect may not translate to humans.

https://insights.ovi...line/7/00076800

For a drug/supplement to have life extension effects on humans, it should improve metabolic health such as increase insulin sensitivity, lower cholesterol, reduce inflammation, etc and with no side effects. Nicotinamide and Rapamycin just don’t fit this profile. Metformin does improve metabolic health, but it has side effects.

So currently, only NR offers a practical way to extend life in humans. Klotho is another one, but there is no commercial Klotho for sale. Gaba seems to be the short term solution.

It's not necessarily lifespan that we're thinking we'll get. It's higher cognitive performance and the feeling of youth from the inhibition of proaging enzymes. This is about maintaining higher levels of neurotransmitters that signal for higher neurosteroid levels and delay brain aging until we get a chance to fix the rest of the aging problem in a sustainable fashion. I'm also interested in the weight loss as deprenyl has several benefits that would increase overall metabolic rate to more youthful levels. In short, I guess taking it is about having less to fix later in life. It's an investment, it'll save you money and improve the efficacy of future rejuvenation treatments that may be very costly. 

Edited by YOLF, 29 October 2017 - 09:54 PM.

[YOLF]

I also read a study that Mao-B doesn’t start to increase until 60 year old.

 

https://www.ncbi.nlm...les/PMC3847108/

 

 

The incidence of PD increases with age, and is associated with significant disability. Its prevalence in patients over 50 years of age is projected to double in the ten most populous nations over the next two decades [1]. Classical motor features of PD such as bradykinesia, rigidity and tremor develop when about 50% of dopaminergic nigrostriatal neurons and about 80% striatal dopamine production are lost [2]. 

 

If 50-80% of neurons have to be lost for the disease to manifest, then there is definitely significant losses of neurons in younger populations. I've read elsewhere that certain types of nerve cell loss begin in the mid teens.

[MikeDC]

It may make sense for someone old to take very low doses to compensate for neuron death.

Prevent neuron death comes first. NR is perfect for this. Many studies show low NAD+
Causes mitochandria dysfunction and neuron death.

https://www.ncbi.nlm...rom=nad neurons

[YOLF]

It may make sense for someone old to take very low doses to compensate for neuron death.

Prevent neuron death comes first. NR is perfect for this. Many studies show low NAD+
Causes mitochandria dysfunction and neuron death.

https://www.ncbi.nlm...rom=nad neurons

I'm sure this stuff helps, but don't you think it should be combined with PQQ as well as deprenyl? Why concentrate on one molecule? More molecules, more benefits and less aging. Deprenyl is very cheap, 90 days for $16 where I found it in either 5 or 10mg doses that could be further split up depending on the person. NR is $1 or so a pill and leads to more budgetary constraints. Does NR have all the same benefits? Does it have as much comparatively independent/devil's advocate research?

Edited by YOLF, 30 October 2017 - 12:06 AM.

[RWhigham]

This new study shows that inhibiting MAO-B is not the mechanism of increasing Rat’s life span. It is related to a previously unknown trigger in rat’s brain to suppress tumor growth. Since rat’s mostly die from tumors while human die mostly from metabolic related diseases, the life extension effect may not translate to humans.  MikeDC

Joseph Knoll's recent work shows that a subcutaneous injection of deprenyl at 1 mcg/kg or 100 mcg/kg increases the activity of catecholamines in rats (shuttle box training of rats used to determine minimum effective doses) but have no effect the release of catecholamines. He found that rats given a weekly subcutaneous injection of catecholamine-releasing tumoragic saline did not develop a tumor when given either of these doses. Knolls latest work is about how the deprenyl prevents the saline induced rat tumors. The effect on catecholamine activity is unrelated to the inhibition of MAO-B. The conclusion that inhibiting excess MAO-B has no effect on lifespan is unsubstantiated.

 

The pharmacological action of selegiline is based on the selective and irreversible inhibition of monoamine oxidase (MAO) type B, resulting in the decreased degradation of dopamine in the central nervous system. ref

 

MAO-B vs age

 MAO-B vs age.jpg   24.52KB   0 downloads

Edited by RWhigham, 30 October 2017 - 12:16 AM.

[MikeDC]

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

[MikeDC]

It may make sense for someone old to take very low doses to compensate for neuron death.

Prevent neuron death comes first. NR is perfect for this. Many studies show low NAD+
Causes mitochandria dysfunction and neuron death.

https://www.ncbi.nlm...rom=nad neurons

I'm sure this stuff helps, but don't you think it should be combined with PQQ as well as deprenyl? Why concentrate on one molecule? More molecules, more benefits and less aging. Deprenyl is very cheap, 90 days for $16 where I found it in either 5 or 10mg doses that could be further split up depending on the person. NR is $1 or so a pill and leads to more budgetary constraints. Does NR have all the same benefits? Does it have as much comparatively independent/devil's advocate research?

I have taken PQQ from life extension for a while and i didn’t feel anything. I have taken many supplements and felt nothing. NR gave me results in two weeks and my health keep improving ever since. I am getting tired telling people how important NR is. Eventually you will find out. Taking any supplements without taking NR first is extremely unwise.

[YOLF]

 

This new study shows that inhibiting MAO-B is not the mechanism of increasing Rat’s life span. It is related to a previously unknown trigger in rat’s brain to suppress tumor growth. Since rat’s mostly die from tumors while human die mostly from metabolic related diseases, the life extension effect may not translate to humans.  MikeDC

Joseph Knoll's recent work shows that a subcutaneous injection of deprenyl at 1 mcg/kg or 100 mcg/kg increases the activity of catecholamines in rats (shuttle box training of rats used to determine minimum effective doses) but have no effect the release of catecholamines. He found that rats given a weekly subcutaneous injection of catecholamine-releasing tumoragic saline did not develop a tumor when given either of these doses. Knolls latest work is about how the deprenyl prevents the saline induced rat tumors. The effect on catecholamine activity is unrelated to the inhibition of MAO-B. The conclusion that inhibiting excess MAO-B has no effect on lifespan is unsubstantiated.

 

The pharmacological action of selegiline is based on the selective and irreversible inhibition of monoamine oxidase (MAO) type B, resulting in the decreased degradation of dopamine in the central nervous system. ref

 

MAO-B vs age

MAO-B vs age.jpg

 

 

 

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

 

 

I don't think anyone is still saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough already?

 

Does BPAP's benefit spectrum do anything else for you at this level?

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

I don't think anyone is saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough?

[YOLF]

 

 

It may make sense for someone old to take very low doses to compensate for neuron death.

Prevent neuron death comes first. NR is perfect for this. Many studies show low NAD+
Causes mitochandria dysfunction and neuron death.

https://www.ncbi.nlm...rom=nad neurons

I'm sure this stuff helps, but don't you think it should be combined with PQQ as well as deprenyl? Why concentrate on one molecule? More molecules, more benefits and less aging. Deprenyl is very cheap, 90 days for $16 where I found it in either 5 or 10mg doses that could be further split up depending on the person. NR is $1 or so a pill and leads to more budgetary constraints. Does NR have all the same benefits? Does it have as much comparatively independent/devil's advocate research?

I have taken PQQ from life extension for a while and i didn’t feel anything. I have taken many supplements and felt nothing. NR gave me results in two weeks and my health keep improving ever since. I am getting tired telling people how important NR is. Eventually you will find out. Taking any supplements without taking NR first is extremely unwise.

 

I felt the same way initially, then I upped the dose to 40mg/day... Taking more can lead to some other interesting benefits, maybe a youthful hypomania? I mixed my own in solution from bulk powder with salt and malic acid and forgot to shake... so not sure how much it was actually, but it felt wonderful, perhaps some loss of concentration to preferring to submit to the feeling of youthful excitement?

[MikeDC]

This new study shows that inhibiting MAO-B is not the mechanism of increasing Rat’s life span. It is related to a previously unknown trigger in rat’s brain to suppress tumor growth. Since rat’s mostly die from tumors while human die mostly from metabolic related diseases, the life extension effect may not translate to humans. MikeDC

Joseph Knoll's recent work shows that a subcutaneous injection of deprenyl at 1 mcg/kg or 100 mcg/kg increases the activity of catecholamines in rats (shuttle box training of rats used to determine minimum effective doses) but have no effect the release of catecholamines. He found that rats given a weekly subcutaneous injection of catecholamine-releasing tumoragic saline did not develop a tumor when given either of these doses. Knolls latest work is about how the deprenyl prevents the saline induced rat tumors. The effect on catecholamine activity is unrelated to the inhibition of MAO-B. The conclusion that inhibiting excess MAO-B has no effect on lifespan is unsubstantiated.

The pharmacological action of selegiline is based on the selective and irreversible inhibition of monoamine oxidase (MAO) type B, resulting in the decreased degradation of dopamine in the central nervous system. ref

MAO-B vs age
MAO-B vs age.jpg

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

I don't think anyone is still saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough already?

Does BPAP's benefit spectrum do anything else for you at this level?

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

I don't think anyone is saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough?

Where did you find the information that dopamine stimulates GnRH? This paper says dopamine is GnRH neuron inhibitor.

https://academic.oup...ropin-Releasing

[Nuke]

Thanks Nuke. Not many commenting on Intra-Nasal Insulin these days. It looks like you are still cycling it. Do you have an opinion about how it is helping you anti-aging wise, or short-term benefits?

 

The IN-insulin I mainly take for it's effect on mood, I seem to be getting a benefit as low as 5UI a day. I don't really feel it acutely, its more of a slight background positivity I get, a feeling of "I can do this". 

 

Long term effects are unfortunately a bit shrouded in mystery, so its one of the things I take I'm a bit worried about. But its seems to have positive effects on Alzheimers and Parkinsons(in rats anyway), Memory and mood improvement in normal humans, increased peripheral insulin sensitivity and protection of beta cells in diabetes T1 patients going for it. It is a growth factor though, so spraying it up my nose daily may have unanticipated effects long term.

 

While I cycle it, I checked through my log, and I have been taking it about 80% of the time the past year, in the beginning at 10-20UI and since July at 5UI.

 

 

For me anti-aging is just on of the aims I'm interested in. Increased cognition is just as important, with mood a subset of it. Also lately getting more into physical capabilities, a big, powerful individual has a lot going for him. It may be as basic as, no use in stopping the aging process and getting beaten to death by someone with a brick. I guess in the end I just want to get very good at everything.  The more aims a supplement/protocol fulfills at a time, the better. Thats why I have some high hopes for Selegiline.

[Heisok]

Thanks Nuke.

[YOLF]

 

 

I don't think anyone is still saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough already?

Does BPAP's benefit spectrum do anything else for you at this level?

 

BPAP is much less selective than Selegiline in MAO-B inhibition. But it is much more effective than Selegiline at life extension on mice. It tell you that the mechanism of action is somewhere else.

I don't think anyone is saying that MAO-B inhibition is the life extension benefit, just that it leads to additional benefits that preserve a healthy physique. Higher dopamine means higher GnRH and it's cascade which prevent and effectively treat obesity, schizo disorders, promote youthful neuroplasticity, demethylate epigenetic changes associated with a spectrum of disease states and more. It's a very powerful mechanism for better general health. This is how it improves healthspan and not just lifespan... We already know that no one here wants a longer lifespan if there isn't also a longer healthspan and youthspan to go along with it. So why try to find drugs that only extend lifespan? Isn't getting old disgusting enough?

 

Where did you find the information that dopamine stimulates GnRH? This paper says dopamine is GnRH neuron inhibitor.

https://academic.oup...ropin-Releasing

 

 

Increasing dopamine increases testosterone, there's lots of evidence of it. Here's the first study that comes up on google in relation to it:

 

The catecholaminergic stimulation of gonadotropin-releasing hormone release by GT1-1 cells does not involve phosphoinositide hydrolysis.

 

 

Gonadotropin-releasing hormone (GnRH) secretion is modulated by a large number of neuromediators, among which catecholamines play a central role. Previous results have shown that both dopamine (DA) and norepinephrine (NE) stimulate GnRH secretion in GT1 neuronal cell lines.

 

I'm sure there's better, but this should be enough to open your eyes to it.

 

Anyways, it's well known that neurons are sensitized to dopamine by testosterone among other things and that the process signals for more testosterone. People use dopamine raising supplements/drugs to raise testosterone. It's about sustainable metabolism and GnRH is the parent molecule of the sex hormones, raising it in healthy individuals whose reproductive system is fully functional will lead to more T/E.

Edited by YOLF, 30 October 2017 - 06:13 PM.

[normalizing]

mike all you do is advertise that crappy NR that i have used for months with zero benefit. can you stop advertising and try to get into the discussion properly?

 

personally , i think BPAP is the way to go since as i said NR sucked for me and selegiline didnt really do much either