731 replies to this topic

[Longevitarian]

This Is More Detailed Report From The DQF Experiment On

Humster Conducted In November 2016. (Part 1)

 

To Get Whole Picture Please Revisit My Previous Postings:

http://www.longecity...m-nyles/page-10

http://www.longecity...m-nyles/page-11

 

To recall major development; HUMster was cured from his hypertension

by DQF intervention, based on multiple blood pressure tests before

and after the intervention.

Moreover the healthy/youthful range of diastolic and systolic pressure continues to

persist until now...indicating,probably permanent rejuvenation of vascular system.

 

On top of this month ago HUMster underwent Echocardiogram , which

tests major parameters of heart muscle, but not vasculature. I received

results just few days ago.

 

To my surprise all parameters of the heart action and diamensions are well

within normal range, with exception of slight diastolic impairment and mild

tricuspid regurgitation with normal right ventricular systolic pressure

(YEY , still have some markers left for future interventions)

Both problems are very minor.

 

What is surprising is that about 9 years ago HUMster was diagnosed

with left ventricle enlargement and heart wall thickening. Both can

be caused accumulation of senescent cells in cardiac muscle among other

reasons.

NO MORE ....BOTH ABNORMALITIES DISAPPEARED,BOTH PARAMETERS

ARE WELL  WITHIN NORMAL RANGE AFTER LAST ECHOCARDIOGRAM.

WOW!!!!!!!

 

At this moment I cannot tell whether HUMster's heart cured on its own or it was

because of DQF intervention,or perhaps because of  previous interventions.

I do not have any Echocardiogram tests done in between (9 years ago and now).

However,what I have is lots of ECG tests, done almost on biweekly basis going 

back more than 10 years.

Unfortunately , not available at this moment.....I have to collect them from

several labs, which will take some time.

 

What I hope is that I will be able to see/pinpoint on the ecg the transition from

pathology to normalcy.

 

If the ECG's will show that the transition from unhealthy to healthy heart

diamensions occured after the DQF intervention , it would be another N1

EVENT. It would be first indication that DQF cures some pathological aspects

of the entire CARDIOVASCULAR System in HUMsters. This hypothesis is 

quite likely true because of its senolytic potential and similar effects in

the experiments on mice published elsewhere.

 

Also Ms HUMster insisted that I will inform that HUMmster's hardness,durability

and ease to evoke the erection consderably improved since DQF. This could be

another marker of improvement of the cardiovascular system. She mentioned

that this keeps her very ,very happy. She would not insist to make it public

if she did not mean it. (WOMEN!!!!)

 

Next posting will deal with the issues pertaining to events immediately before and

after dosing.

 

Thank you for your attention.

Edited by Longevitarian, 29 March 2017 - 02:15 AM.

[PeaceAndProsperity]

To recall major development; HUMster was cured from his hypertension

by DQF intervention, based on multiple blood pressure tests before

and after the intervention.

Moreover the healthy/youthful range of diastolic and systolic pressure continues to

persist until now...indicating,probably permanent rejuvenation of vascular system.

Hypertension caused by arterial plaque deposits or calcification?

 

[Longevitarian]

Hi PeaceAndProsperity

 

I am leaving the answer to your question for discussion on the board. My understanding

of hypertension is that it can result from many factors. Those include: garbage accumulation,

hormonal, neurophysiological mechanisms and immune system. This list does not exhaust all

possible factors, just points to some important ones....

The systolic/diastolic blood pressure integrates all those effects creating simple measure

indicating state of the health of not only cardiovascular system but also those other systems.

So when the measure is off the doctor does other tests to figure out where the imbalance

comes from. However when the dia/sys is within the norm it is assumed that all

systems affecting it are also functionning properly (case closed with most of

the docs)

 

Below article gives:

 

"Evidence For Senescent Cells To Promote Vascular Calcification"

https://www.fightagi...-calcification/

 

And

 

"Hypertension Primer"    for those who would like to explore hypertension in greater detail :

https://books.google...nescent&f=false

 

Cheers

[mikey]

Hi PeaceAndProsperity

 

I am leaving the answer to your question for discussion on the board. My understanding

of hypertension is that it can result from many factors. Those include: garbage accumulation,

hormonal, neurophysiological mechanisms and immune system. This list does not exhaust all

possible factors, just points to some important ones....

The systolic/diastolic blood pressure integrates all those effects creating simple measure

indicating state of the health of not only cardiovascular system but also those other systems.

So when the measure is off the doctor does other tests to figure out where the imbalance

comes from. However when the dia/sys is within the norm it is assumed that all

systems affecting it are also functionning properly (case closed with most of

the docs)

 

Below article gives:

 

"Evidence For Senescent Cells To Promote Vascular Calcification"

https://www.fightagi...-calcification/

 

And

 

"Hypertension Primer"    for those who would like to explore hypertension in greater detail :

https://books.google...nescent&f=false

 

Cheers

 

Very interesting about the potential vascular benefits. About two months ago I did 300 mg D with about 1,500 mg liposomal quercitin one time and did feel an odd change in my heartbeat that went away after about 8 days - not fun when it was happening. 

Then about 10 days ago I did 50 mg of D with lots of liposomal and mycellized Q.

Rather suddenly, seven days ago my blood pressure began to be quite low, like that of a teenager.

113/73, 105/65, 100/60 - readings like this, even at night when my BP tended to increase.

 

My BP had been increasing for the last ten years, although over the last four years I have brought it down with meds, to high normal (~135/85) or slightly better. At worst it could hit 160/100 if left unchecked. 

 

A confounding variable is that I've been taking GDF11 since December. However, I've been exposed to it for this long time period with no change in BP until I did the D&Q.

 

This points at the D&Q, so I am considering how much to use to "clean house" and how often.

 

I've read several different dosing schemes for D&Q. From what I've read more side-effects might be experienced above 100 mg of D at a time. And it seems like it should be taken intermittently.

 

I haven't had time to catch up on reading this this board in its entirety. 

 

Can someone clarify please clarify optimal dosing for D&Q so that side-effects are minimized?

Note please - I use liposomal and/or mycellized quercitin, so less is needed than when taking plain quercitin. 

Thanks, in advance.

[DareDevil]

Hi Mikey,

 

That is an interesting account of the effects of D+Q on your blood pressure. It's always nice when substances taken for another purpose help with another pathology unexpectedly.

 

I'm impressed that you tried 300mg of Dasatinib, as 100mg feels very strong to me. However I am older than you and possibly have way more senescent cells to eliminate, which might mean that it is more active in my system? In your much younger body possibly the D+Q cruises around patrolling for an occasional defective cell? Obviously this is pure speculation.

 

It's great that you tried 50mg of Dasatinib. That is a safe dose with regards to side effects. When I took 40mg/day of Sprycel with the same active ingredient in December 2015, I took 40mg with regular Quercetin daily for two weeks and felt neither tired nor feverish.

 

At 100mg I get a strong fever. I took a single dose at this level a week ago and had to call in sick, unable to drag myself to work. So now I will either take it on a weekend, when I can relax at home, or find ways to reduce the fever symptoms. This is why I brought up Chelation in this thread, not to sidetrack the discussion but because Chelation might be a way to reduce the harsh sides of D+Q?

 

To keep the focus here on Dasatinib, I will start a Chelation for Senolytics thread to deal with that issue separately. At present I am experimenting with 2 grams of L-Carnosine before and after taking D+Q and will report back. It is interesting because not only does it remove heavy metals - useful to absorb them form senescent cells before they ooze into the bloodstream - this substance also reduces glycation which I suspect to occur after old cell genocide:

 

QUOTE:

 

"...glycation, which can be described as "caramelization" of proteins in the bloodstream and in nerve tissue by excessive levels of sugar. When proteins join with glucose, they cease to function, and they release free radicals that can spread tissue damage even further."

 

http://www.nutrition...e-benefits.html

 

Once I have tested the effects of using this before and after D+Q I will try other chelators to see which might reduce the feverish state that ensues.

 

Cheers,

 

DareDevil

[Andey]

Hi Mikey,

 

That is an interesting account of the effects of D+Q on your blood pressure. It's always nice when substances taken for another purpose help with another pathology unexpectedly.

 

I'm impressed that you tried 300mg of Dasatinib, as 100mg feels very strong to me. However I am older than you and possibly have way more senescent cells to eliminate, which might mean that it is more active in my system? In your much younger body possibly the D+Q cruises around patrolling for an occasional defective cell? Obviously this is pure speculation.

 

It's great that you tried 50mg of Dasatinib. That is a safe dose with regards to side effects. When I took 40mg/day of Sprycel with the same active ingredient in December 2015, I took 40mg with regular Quercetin daily for two weeks and felt neither tired nor feverish.

 

At 100mg I get a strong fever. I took a single dose at this level a week ago and had to call in sick, unable to drag myself to work. So now I will either take it on a weekend, when I can relax at home, or find ways to reduce the fever symptoms. This is why I brought up Chelation in this thread, not to sidetrack the discussion but because Chelation might be a way to reduce the harsh sides of D+Q?

 

To keep the focus here on Dasatinib, I will start a Chelation for Senolytics thread to deal with that issue separately. At present I am experimenting with 2 grams of L-Carnosine before and after taking D+Q and will report back. It is interesting because not only does it remove heavy metals - useful to absorb them form senescent cells before they ooze into the bloodstream - this substance also reduces glycation which I suspect to occur after old cell genocide:

 

QUOTE:

 

"...glycation, which can be described as "caramelization" of proteins in the bloodstream and in nerve tissue by excessive levels of sugar. When proteins join with glucose, they cease to function, and they release free radicals that can spread tissue damage even further."

 

http://www.nutrition...e-benefits.html

 

Once I have tested the effects of using this before and after D+Q I will try other chelators to see which might reduce the feverish state that ensues.

 

Cheers,

 

DareDevil

 

With all respect, I think you are going in a wrong direction while explaining cause of your malaise.

Most probably its a inflammation caused by mass destruction of senescent cells. Anyway chelation is more of prolonged process that supposed to help in a long run, it would not help you in days, frankly you would not notice its effects in such period.

I think you would be better off if add few glutathione IV shots after D+Q (probably after some signifacant delay). It would calm immune system and boost greatly liver detox capabilities. Its much more effective for inflamation then anything else.  Females use glutathione IV as a skin beauty treatment so I believe its available in some beauty salons etc. You could buy it youself but administring it IV by youself could go messy way ) IM injection is fine but there is doubt whether it is as effective as IV one.

[DareDevil]

Thanks Andey,

 

Thanks for your advice, I will definitely try to find injectable glutathione. However I will self-inject versus Intra-Venous infusion, as I'm no billionaire like Peter Nygaard with a personal medical lab. BTW I have added your diagnosis of this suspected cause of the Dasatinib induced fever to a new thread recently posted in this forum section. Thanks for reposting your recommendations there?

 

http://www.longecity...enolytic-drugs/

 

Cheers,

 

DareDevil

[Nate-2004]

It is likely stronger for some of you because you are a poor metabolizer of certain medications. CYP3A4 is relevant here as noted on their site. 23 and Me informed me that I am also a poor metabolizer genetically. These differences in gene expression can explain the variation in how different people respond to a lot of different things.

[mikey]

Thanks Andey,

 

Thanks for your advice, I will definitely try to find injectable glutathione. However I will self-inject versus Intra-Venous infusion, as I'm no billionaire like Peter Nygaard with a personal medical lab. BTW I have added your diagnosis of this suspected cause of the Dasatinib induced fever to a new thread recently posted in this forum section. Thanks for reposting your recommendations there?

 

http://www.longecity...enolytic-drugs/

 

Cheers,

 

DareDevil

 

Increasing glutathione is a simple matter that doesn't require needles. Take the precursor N-acetyl cysteine (NAC), which converts very well into glutathione.

 

This has been clearly documented, including a placebo-controlled study from the Herzenberg Lab at Stanford, where they gave HIV+ people between 3,200 and 8,000 mg/day of NAC/day. Glutathione increases were directly associated with reduced mortality.
________________________________________

 

LAH #448
De Rosa, S. C., Zaretsky, M. D., Dubs, J. G., Roederer, M., Anderson, M., Green, A., Dipendra Mitra, M., Watanabe, N., Nakamura, H., Tjioe, I., Deresinski, S. C., Moore, W. A., Ela, S. W., Parks, D., Herzenberg, L. A. and Herzenberg, L. A. (2000). "N-acetylcysteine (NAC) replenishes glutathione in HIV infection." European Journal of Clinical Investigation: 30(10):915-929.Abstract

Background Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. 

Design Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.

Subjects HIV-infected, low GSH, CD4 T cells < 500 mL -1 , no active opportunistic infections or other debilitation; h=81. Study conducted prior to introduction of protease inhibitors.

Results Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P =0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and b2-microglobulin levels, also increased in the NAC-treated subjects (P ‹0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.

Conclusion. NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.Keywords glutathione, GSH, GSH deficiency, HIV, N-acetylcysteine, NAC Review of article LAH #448.

_________________________________________________

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

Edited by mikey, 01 April 2017 - 03:23 AM.

[Andey]

 

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

 

 

NAC driven increase is nothing compared to IV Glutathione. Trust me Ive tried both intensively ) I hardly notice any effect of NAC on inflammation but IV G is definitely noticeable.

Ive nothing against NAC thought it is a good addition to long term stack.

[ClarkSims]

There is a thread about the FOXO4 peptide inhibitor study. I just posted several items about FOXO inhibition.

http://www.<span>lon...span>/?p=811050

Edited by ClarkSims, 01 April 2017 - 04:37 PM.

[Nate-2004]

This is getting off topic from the group buy but oh well, it's being shipped now anyway. 

 

Isn't glutathione a thing that is good to have but not in excess? Too much is bad and too little is bad?

 

Also why would FOXO3 inhibition be good? Isn't it the opposite?

[mikey]

This is getting off topic from the group buy but oh well, it's being shipped now anyway. 

 

Isn't glutathione a thing that is good to have but not in excess? Too much is bad and too little is bad?

 

 

Good point - most nutrients have an optimal range, where the effects are optimal and there is neither too little nor too much. With some nutrients, such as iron, the side effects presented by high doses can be significant. And then for some, like vitamin C, there are no cytotoxic effects, just the well-known "bowel-tolerance" effect, where too much oral vitamin C causes diarrhea. Other than that vitamin C is safer than milk or aspirin or dozens of other nutrients.

 

There are data that show that there is a potential for negative effects with high-dose glutathione or NAC. However, how frequently this happens and at what dosing should be considered.

 

For the Herzenberg HIV/NAC studies to occur, an Institutional Review Board (IRB) had to approve NAC dosing of 3,200 to 8,000 mg/day. This is an indication of the IRB seeing considerable safety at these high doses.

 

I have been taking high dose NAC regularly since the early '90's with no experience of any of the potential side-effects. However, one must consider that each individual is different. Therefore, each individual should do their own due diligence and make a dosing decision based on analysis of the available data. 

 

As a point of reference, even water can cause side-effects or even be lethal if one drank too much of it or found themselves swimming in the middle of the ocean. 

 

The mouse LD50 of oral NAC is reported to be about 8,000 mg/kg. For oral glutathione the LD50 is reported to be about 5,000 mg/kg.

 

So, while adverse effects at high doses should be considered, it seems that the potential for adverse effects to occur at even relatively high doses, such as the 1,800 mg that I take on occasion, is low.

 

From the days when I partied occasionally I can report that high-dose NAC kills hang-overs in an amazing way. You can feel like crap and take NAC and feel great in less than an hour.

 

Based on thousands of published studies and personal experience, long ago I became an enthusiast for higher, more optimal potencies. After years of taking high potencies of various nutrients with no problems I did experience an adverse effect, hypothyroidism, after taking high-dose alpha lipoic acid for several years. So, all things should be carefully considered, even for the safest of nutrients.  

[ClarkSims]

This is getting off topic from the group buy but oh well, it's being shipped now anyway. 

 

Isn't glutathione a thing that is good to have but not in excess? Too much is bad and too little is bad?

 

Also why would FOXO3 inhibition be good? Isn't it the opposite?

 

I agree. I was attempting to reply to VP's, post on these senolytics,  http://www.cell.com/...8674(17)30246-5   which are FOXO4 down-regulators. I will repost, with the correct quote to add clarify.  I was hoping people would talk about the new FOXO4 down-regulators in the thread devoted to that piece of research.  You can read the article (please read it, I would appreciate as many eyes looking at this, and as many brains thinking about it as possible). But to paraphrase, the authors believe that senescent cells are primed for apoptosis, but the FOXO4 gene is stuck in maximum RNA production mode. The FOXO4 down regulator cancels out the mistaken up-regulation, and the cells then commit apoptosis.

Edited by ClarkSims, 02 April 2017 - 01:16 AM.

[Logic]

Increasing glutathione is a simple matter that doesn't require needles. Take the precursor N-acetyl cysteine (NAC), which converts very well into glutathione.

 

This has been clearly documented, including a placebo-controlled study from the Herzenberg Lab at Stanford, where they gave HIV+ people between 3,200 and 8,000 mg/day of NAC/day. Glutathione increases were directly associated with reduced mortality.
________________________________________

 

LAH #448
De Rosa, S. C., Zaretsky, M. D., Dubs, J. G., Roederer, M., Anderson, M., Green, A., Dipendra Mitra, M., Watanabe, N., Nakamura, H., Tjioe, I., Deresinski, S. C., Moore, W. A., Ela, S. W., Parks, D., Herzenberg, L. A. and Herzenberg, L. A. (2000). "N-acetylcysteine (NAC) replenishes glutathione in HIV infection." European Journal of Clinical Investigation: 30(10):915-929.Abstract

Background Glutathione (GSH) deficiency is common in HIV-infected individuals and is associated with impaired T cell function and impaired survival. N-acetylcysteine (NAC) is used to replenish GSH that has been depleted by acetaminophen overdose. Studies here test oral administration of NAC for safe and effective GSH replenishment in HIV infection. 

Design Oral NAC administration in a randomized, 8-week double-blind, placebo-controlled trial followed by optional open-label drug for up to 24 weeks.

Subjects HIV-infected, low GSH, CD4 T cells < 500 mL -1 , no active opportunistic infections or other debilitation; h=81. Study conducted prior to introduction of protease inhibitors.

Results Whole blood GSH levels in NAC arm subjects significantly increased from 0.88 mM to 0.98 mM, bringing GSH levels in NAC-treated subjects to 89% of uninfected controls (P =0.03). Baseline GSH levels in the placebo group (0.91) remained essentially the same during the 8 week placebo-controlled trial. T cell GSH, adjusted for CD4 T cell count and b2-microglobulin levels, also increased in the NAC-treated subjects (P ‹0.04). Adverse effects were minimal and not significantly associated with NAC ingestion.

Conclusion. NAC treatment for 8 weeks safely replenishes whole blood GSH and T cell GSH in HIV-infected individuals. Thus, NAC offers useful adjunct therapy to increase protection against oxidative stress, improve immune system function and increase detoxification of acetaminophen and other drugs. These findings suggest that NAC therapy could be valuable in other clinical situations in which GSH deficiency or oxidative stress plays a role in disease pathology, e.g. rheumatoid arthritis, Parkinson's disease, hepatitis, liver cirrhosis, septic shock and diabetes.Keywords glutathione, GSH, GSH deficiency, HIV, N-acetylcysteine, NAC Review of article LAH #448.

_________________________________________________

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

 

NAC both protects against Hepatotoxicity and decreases the effectiveness of of Dasatinib.
This makes it difficult to know if its a good idea to use it concomitantly.
I advise sticking with previously ascertained HED of Dasatinib.
(Personally I am leaning toward HED + 20%)

 

...Here we found that Dasatinib dramatically increased the level of reactive oxygen species (ROS) in hepatocytes, reduced the intracellular glutathione (GSH) content, attenuated the activity of superoxide dismutase (SOD), generated malondialdehyde (MDA), a product of lipid peroxidation, decreased the mitochondrial membrane potential, and activated nuclear factor erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinases (MAPK) related to oxidative stress and survival. These results confirm that oxidative stress plays a pivotal role in Dasatinib-mediated hepatotoxicity. N-acetylcysteine (NAC), a typical antioxidant, can scavenge free radicals, attenuate oxidative stress, and protect hepatocytes against Dasatinib-induced injury. Thus, relieving oxidative stress is a viable strategy for reducing Dasatinib-induced hepatotoxicity...

https://www.ncbi.nlm...pubmed/22538170

 

...Protective factors against hepatotoxicity, including vitamin C, glutathione, tiopronin and N-acetylcysteine (NAC) [23-25], have been shown to reduce the anticancer activity of anticancer drugs....

...Recently, the themes of oxidative stress and autophagy have been brought together. A diverse range of stimuli that induce both ROS and autophagy have been described and autophagy induction by these agents is antagonized by antioxidants.[32, 33] Meanwhile, antioxidants such as NAC inhibited mTOR signaling and diminished oxidative stress mediated damage in several diseases by activating autophagy.[34, 35] For this reason, we tested whether dasatinib also increase oxidative stress, and found ROS was up-regulated. However, ROS pan scavenger NAC blocked both autophagy and hepatotoxicity induced by dasatinib(Supporting Fig.3). In addition, NAC even reduced the anticancer activity of dasatinib(Supporting Fig.4), suggesting that these pan oxidative stress inhibitors may be limited in the context of liver injury caused by dasatinib.

https://www.ncbi.nlm...les/PMC4467432/

 

Google results for: 

N-acetylcysteine Dasatinib:  

(I suggest everyone try this!    )
https://www.google.c...ine Dasatinib&*

 

I also note that the half life of Dasatinib is 3 to 6 hours, with 3 to 5 hours mentioned most:
https://www.google.c...chrome&ie=UTF-8
This info seems to have been ignored by those taking more than one intermittent dose.
Based in this I would take a 2nd dose 5-6 hrs later if dosing more than once in a row.
This is also around the time I would start taking NAC and other antioxidants, as well as stem and telomerase activators.

[DareDevil]

Hi friends,

 

Maybe it's better to discuss what adjuncts we use with Dasatinib and other Senolytic drugs in the decated thread here:

 

Managing the Sequels of Senolytic Drugs

http://www.longecity...enolytic-drugs/

[Logic]

There seems to be some misunderstanding regarding my posts on Chelation being important.
It is true that the metals in senescent cells, killed of by apoptosis mostly, not necrosis, would place an extra load on lysosomes.

(Lysosomes use acid to dissolve cellular garbage and metals use up a lot of acid and 'fizz', damaging Lysosomes)
But this is not the reason for my posting.

Heavy/metals not only cause senescence faster, they stop senescent cells from 'apoptosis'.
Thus the clearance of heavy/metals, by itself, can be considered senolytic... 

 

 

Let me reiterate the important role of heavy/metals in catalysing glycation and the role AGEs have in aging, as well as their role in senescence.

Catalyst: A substance that causes or accelerates a chemical reaction without itself being affected..!

ie:

Everything you eat, drink and even breath contains trace amounts of heavy/metals, not to mention fillings!
As they aren't themselves used up, they build up over the years accelerating senescence and AGE formation, which itself accelerates senescence..!

In fact I would go so far as to say that they speed up these processes to faster than they are naturally cleared from they system, at around the age you would currently like to be!

 

But there is no evidence that glycation is somehow released from, or increased by, senescent cells upon their demise.
The only connection I can think of would be increased inflammation and ROS from while they are still alive.

 

 

Another big reason for senescent cells not dying off is infection by pathogens.
Pathogens like CMV, the immune system killer, which keep cells that should have died alive, for their own nefarious reasons.
Note the effect of Quercetin on virally infected cells to back this up...

ie:  Drugs that kill such infected cells, like DRACO, Bavituximab, etc might be considered the most effective and selective senescent cell killers known..!?

 

 

Yet another reason for cellular senescence is telomere attrition, for which there are several, previously discussed, telomerase activators.

Edited by Logic, 02 April 2017 - 01:50 PM.

[Nate-2004]

There seems to be some misunderstanding regarding my posts on Chelation being important.
It is true that the metals in senescent cells, killed of by apoptosis mostly, not necrosis, would place an extra load on lysosomes.

(Lysosomes use acid to dissolve cellular garbage and metals use up a lot of acid and 'fizz', damaging Lysosomes)
But this is not the reason for my posting.

Heavy/metals not only cause senescence faster, they stop senescent cells from 'apoptosis'.
Thus the clearance of heavy/metals, by itself, can be considered senolytic... 

 

 

Let me reiterate the important role of heavy/metals in catalysing glycation and the role AGEs have in aging, as well as their role in senescence.

Catalyst: A substance that causes or accelerates a chemical reaction without itself being affected..!

ie:

Everything you eat, drink and even breath contains trace amounts of heavy/metals, not to mention fillings!
As they aren't themselves used up, they build up over the years accelerating senescence and AGE formation, which itself accelerates senescence..!

In fact I would go so far as to say that they speed up these processes to faster than they are naturally cleared from they system, at around the age you would currently like to be!

 

But there is no evidence that glycation is somehow released from, or increased by, senescent cells upon their demise.
The only connection I can think of would be increased inflammation and ROS from while they are still alive.

 

 

Another big reason for senescent cells not dying off is infection by pathogens.
Pathogens like CMV, the immune system killer, which keep cells that should have died alive, for their own nefarious reasons.
Note the effect of Quercetin on virally infected cells to back this up...

ie:  Drugs that kill such infected cells, like DRACO, Bavituximab, etc might be considered the most effective and selective senescent cell killers known..!?

 

 

Yet another reason for cellular senescence is telomere attrition, for which there are several, previously discussed, telomerase activators.

 

Doesn't L-Carnosine chelate heavy metals? I just take that regularly, ~500mg with each meal per day.

[aribadabar]

Doesn't L-Carnosine chelate heavy metals? I just take that regularly, ~500mg with each meal per day.

 

 

I think Carnosine needs to be taken away from meals as it chelates not only heavy metals but beneficial ones (from food) as well.

Intake on an empty stomach/before bedtime is better IMO.

[DareDevil]

While we're still experimenting with dosages for D+Q and trying to establish what other substances to use before, during and after intake, to formulate a Protocol, for the time being this thread seems like the best place to share info regarding future Senolytic substances we may wish to source and test.

 

Logic mentioned Navitoclax, which has been used as a drug in cancer treatment. Thanks to this, similarly to Dasatinib, we have indications of human dosage that are well tolerated as established in clinical trials. It is possible that we'd need less strong doses without a cancer to combat when using it only to kill senescent cells. Below a study show its safety profile. They tried daily dosages from 10 mg to 440 mg, with varying results, see the table below.

 

https://www.ncbi.nlm...25495/table/T1/

 

It was stated that "315 mg was identified as the safe tolerated dose for the intermittent schedule"

 

https://www.ncbi.nlm...les/PMC3025495/

 

Their clinical trial pursued with a 150 mg lead dose, followed by 325 mg continued dosing. We can deduce from this that human trials using Navitoclax episodically for Senolytic purposes might be undertaken with a measure of safety, and with potential success at dosages of 100 mg/day without significant health risks. While mainstream laboratories price Navitoclax at approximately $1000/100mg, the best quote I received was for $1000/1g which comes to $1/mg. Knowing how many 100mg doses would be required, could help determine cost-effectiveness of a Group Buy. At current pricing it still seems high, unless it is active at low doses.

 

Similar dosages were used to combat cancer with Dasatinib, and I found positive but limited effectiveness in a two week run at 40mg/day. Making double that what I would consider an effective dose. For this reason, rightly or wrongly, I have assumed that for the purposes of eliminating senescent cells, one would be able to extrapolate the dosage data from Dasatinib to Navitoclax until more is known. This would make it a potential candidate to wealthier members here, but not quite yet in broader Group Buy territory. If Logic has the opportunity to find lower pricing, however, we may soon be able to also try this new substance in our arsenal of anti-aging therapies.

 

DareDevil

[Logic]

Doesn't L-Carnosine chelate heavy metals? I just take that regularly, ~500mg with each meal per day.

 

There is evidence of Acetyl L-Carnosine being a good AGE blocker and even a breaker/chelator with the eye drops dissolving cataracts.
IIRC the problem with it is. as with most things, it is quickly metabolised somewhere along the way to cells when taken orally.
There is info on how to circumvent that here somewhere, but as the eye drops take 2 years IIRC to show improvement I'm guessing its not a very powerful chelator.

The procedure when you down a tin of lead based paint or something is Intravenous chelation therapy.
I would say that this is the most effective way of dumping heavy metals in a hurry and shows some very interesting results that make big pharma very nervous (A good sign), but is not as effective as I would like.

Reasons for ineffectiveness:

• IIRC the hucksters will stick a Calcium EDTA drip in your arm for an hour as Calcium EDTA is far less likely to kill you by chelation vital calcium.  The real deal uses plain EDTA for 3 hours, with careful Calcium monitoring and level correction.
• Extracellular chelators do a good job of cleaning metals from the extracellular matrix, but don't get into cells well, if at all.  There is some literature of showing additive and synergistic effects from combining intra and extracellular chelators.
• Different chelators clean different metals, but no one Chelator cleans them all.  They also clean necessary minerals which then have to be supplemented.
• Heavy metals cause damage locally.  If a particle is chelated, but that chelator itself is metabolised, dropping that particle, before that particle is excreted. it will cause the same amount of damage again, in a new area.  Thus knowing the half life of all the chelators used, so that the correct dosage schedule is implemented, is critical.

As you can imagine, working out a safe, additive/synergistic chelation therapy/stack with what to take (by drip in some cases), when to take it and how much to take, is a major task!  Especially if AGE breakers that don't work by chelation are added to the mix.

A task for which not all the animal research is complete, but given time and possibly a good team of like minded researchers, is altogether possible.

If one were to come up with such a stack I beleive it would be a game changer... of the type worth more than a mere post on a forum...

[Nate-2004]

Supposedly if you take enough carnosine, 500mg or more 3x daily, it's enough to overwhelm the enzymes that metabolize it. I was just trying to understand how it relates to chelation.

[DareDevil]

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

 

I also note that the half life of Dasatinib is 3 to 6 hours, with 3 to 5 hours mentioned most:

https://www.google.c...chrome&ie=UTF-8
This info seems to have been ignored by those taking more than one intermittent dose.
Based in this I would take a 2nd dose 5-6 hrs later if dosing more than once in a row.
This is also around the time I would start taking NAC and other antioxidants, as well as stem and telomerase activators.

 

 

Hi Logic,

 

Point well taken. I have listened and decided to try such a protocol each time adding 1000% Quercetin per mg of Dasatinib (1/D+10Q).

 

Yesterday at 6pm I took 100mg of Dasatinib, then a second 100mg dose at midnight, a third 100mg dose at 6am, followed by a 4th dose of 100mg Dasatinib at noon. This makes for 400mg/24hours, which is fairly high dosage, making this a short run trial lasting a day or two, maybe three at maximum.

 

I will report back but so far I have had ZERO FEVER using this protocol. I do not know whether it is because the D+Q stay active in the bloodstream and prevent the fever from kicking in. Instead, were the worst of the toxins possibly for the most part evacuated in my previous trials with D+Q, those that led to strong bouts of fever?

 

Or was it because preceding this intake I took supplements which may have chelated and otherwise cleansed senescent cells prior to their lysis? The supplements I took for just a few days each were 1g/day liposomal Vitamin C, high absorption full spectrum Curcumin, pharmaceutical grade Sulphoraphane, L-Carnosine powder, Asthanxin powder and Pterostilbene.

 

I'll keep you posted on any results.

 

DareDevil

[Logic]

Dasatinib Progress report:

The lab started posting the D yesterday en route home after work and should post the rest today unless held up at work.

I am going to start sending people their Tracking #s tonight. (19h45 here)

[Logic]

 

 

NAC is cheap. I generally take the Jarrow NAC-Sustain @ 1,800 mg a couple-few times a day. Of supplements NAC is one that truly provides protective anti-ageing  benefits.

 

I also note that the half life of Dasatinib is 3 to 6 hours, with 3 to 5 hours mentioned most:

https://www.google.c...chrome&ie=UTF-8
This info seems to have been ignored by those taking more than one intermittent dose.
Based in this I would take a 2nd dose 5-6 hrs later if dosing more than once in a row.
This is also around the time I would start taking NAC and other antioxidants, as well as stem and telomerase activators.

 

 

Hi Logic,

 

Point well taken. I have listened and decided to try such a protocol each time adding 1000% Quercetin per mg of Dasatinib (1/D+10Q).

 

Yesterday at 6pm I took 100mg of Dasatinib, then a second 100mg dose at midnight, a third 100mg dose at 6am, followed by a 4th dose of 100mg Dasatinib at noon. This makes for 400mg/24hours, which is fairly high dosage, making this a short run trial lasting a day or two, maybe three at maximum.

 

I will report back but so far I have had ZERO FEVER using this protocol. I do not know whether it is because the D+Q stay active in the bloodstream and prevent the fever from kicking in. Instead, were the worst of the toxins possibly for the most part evacuated in my previous trials with D+Q, those that led to strong bouts of fever?

 

Or was it because preceding this intake I took supplements which may have chelated and otherwise cleansed senescent cells prior to their lysis? The supplements I took for just a few days each were 1g/day liposomal Vitamin C, high absorption full spectrum Curcumin, pharmaceutical grade Sulphoraphane, L-Carnosine powder, Asthanxin powder and Pterostilbene.

 

I'll keep you posted on any results.

 

DareDevil

 

 

Sounds good DareDevil.  I look forward to your report.

I noted interesting effects from concomitant dosing of Pterostilbene and Quercetin in vivo on the relevant genes B, but haven't properly read the full paper or reached any conclusions:

https://www.ncbi.nlm...90314/table/T5/

Full paper:

https://www.ncbi.nlm...les/PMC1490314/

 

The effect of vitamin C on cancerous stem cell growth is also very interesting:
http://www.longecity...ndpost&p=811232
It's probably something to start taking around the half life of one's last dose, but may prevent the effect/s of D etc if used concomitantly.

 

There is evidence that curcumin is a senolytic at the correct dosage:
http://www.longecity...crophagy/page-3

https://cse.google.c...scent curcumin[

IIRC turmerones, other molecules in turmeric, help its absorption and are cofactors to its effect too. 

 

At a guess I would say that your lack of a fever this time is probably due to a lack of senescent cells causing a Herxheimer effect.
Your pre supp regimen may also have had an effect as can be surmised from the above.
I recall Pterostilbene protecting blood, so it may be a very good option for concomitant or post D or N use.
 

Hemolytic disorders include a broad spectrum of hereditary and acquired conditions that range from mild to severe clinical outcomes [50]. Hemolytic anemias, irrespective of etiology, are exacerbated by exposure to ROS, which produces both internal and external damage to red blood cells (RBCs), accelerating the process of hemolysis. Studies have shown that ROS-induced hemolysis is a modifiable event that can be alleviated with antioxidant treatment [51]. Specifically, treatments with blueberry extract and pterostilbene have been shown to protect RBCs against ROS-induced hemolysis indicating a possible therapeutic effect in the treatment of hemolytic anemia.
https://www.hindawi....cl/2013/575482/

 

 

Edited by Logic, 04 April 2017 - 07:27 PM.

[DareDevil]

Update:

 

1. I wouldn't recommend dosing as high as 4 x 100gm/24hours = 400mg

2. I found that dosing every 6 hours was less harsh and more effective

3. I had no flu symptoms but had high temperature once half-life ended

4. Similarly to before I feel tissue shrinkage and somewhat rejuvenated

 

Next time, I may try 3 x 100mg over 18 hours i.e. dosing every 6 hours = 300mg

Or spreading it out with 6 x 70mg over 36 hours, dosing every 6 hours = 420mg

 

I found that intense intake for a short period was more beneficial than slower intake over a longer period of time. Logic probably is onto something when he says that we must maintain product suspended in our bloodstream for a longer period than 5 or 6 hours. Keeping levels high makes a difference in my perceived result. I was led to try this by his convincing argument, but also by Mikey's trial with high dose single intake of 300mg which had violent impact but also some lasting benefits. High doses might be most useful, but spreading them out in 6 hour intervals makes them less harsh in their consequences. It also allows the patient to stop intake at any stage if they feel it's too much. However, please note that, in my modest experience, the strongest side-effects happen once the half-life is over and you're starting to experience the consequences.

 

DareDevil

[Nate-2004]

Considering the half life then I may dose 75mg twice a day each time with 1500 mg Q, for 5 days every 6 months or so. Pretty sure that's all that would be necessary. I won't be doing or taking anything else at all for that time period. No NR, nothing, not even vitamin D I don't think. I might not even work out at the gym or use the sauna. I realize the only listed concern is CYP3A4 inhibition (bioperine being an inhibitor), but not sure if there wouldn't be any other interactions with the ridiculous number of supplements I take.

 

Besides, I could use a 5 day break from anti-aging regimens so that I can do this anti-aging regimen. 

Edited by Nate-2004, 05 April 2017 - 01:31 PM.

[SearchingForAnswers]

Please somebody,

 

What is the "F" in D+Q+F?

 

Fisetin?

Edited by SearchingForAnswers, 05 April 2017 - 04:47 PM.

[ClarkSims]

Please somebody,

 

What is the "F" in D+Q+F?

 

Fisetin?

 

Fasting

Robert Longo is good source for information on fasting.

[mikey]

Update:

 

1. I wouldn't recommend dosing as high as 4 x 100gm/24hours = 400mg

2. I found that dosing every 6 hours was less harsh and more effective

3. I had no flu symptoms but had high temperature once half-life ended

4. Similarly to before I feel tissue shrinkage and somewhat rejuvenated

 

Next time, I may try 3 x 100mg over 18 hours i.e. dosing every 6 hours = 300mg

Or spreading it out with 6 x 70mg over 36 hours, dosing every 6 hours = 420mg

 

I found that intense intake for a short period was more beneficial than slower intake over a longer period of time. Logic probably is onto something when he says that we must maintain product suspended in our bloodstream for a longer period than 5 or 6 hours. Keeping levels high makes a difference in my perceived result. I was led to try this by his convincing argument, but also by Mikey's trial with high dose single intake of 300mg which had violent impact but also some lasting benefits. High doses might be most useful, but spreading them out in 6 hour intervals makes them less harsh in their consequences. It also allows the patient to stop intake at any stage if they feel it's too much. However, please note that, in my modest experience, the strongest side-effects happen once the half-life is over and you're starting to experience the consequences.

 

DareDevil

 

It should be noted that the beneficial effect of lower blood pressure since my use of D&Q happened even though I did not stop taking the numerous antioxidant supplements, like NAC, that I take. I imagine that I could have experienced even more of an effect. 

 

Next time I will be very careful with what I take and when I take it to optimize the effects on senescent cells.

 

For me, no more high doses all at once. The weird heart beat that lasted all day and night for about 8 days was not OK. I will likely do some version of every 5-6 hours at 100 mg. I am still watching what people experience here before I do another round.

 

I should also note that after D&Q I lost about ten pounds in about two weeks, which was desirable. Lighter, leaner lives longer.

 

Additionally, my facial skin looks younger. There is a slight browning of my salt and pepper hair, but I am not sure that this is because of D&Q.

 

Again, I value unprompted comments from people that know me well. I was told that I look younger by two people who said that they noticed a change in a quick few days, both noted seeing some color - a bit of brown - in my hair.