731 replies to this topic

[Longevitarian]

Fasting, on its own, is a good strategy to deal with the garbage accumulating in the body.

During fasting the body is forced to search for nutrients and they can readily come from

recycled bad cells as well as from processing of the waste accumulating inside good cells and within

extracellular space. Those are ancient mechanisms evolutionary conserved in all organisms.

The way it is done is a bit complex , but to say briefly it involves mechanisms from within the cells

such as apoptosis , autophagy and proteolysis as well as those ouside of the cell, mostly via

the immune system.  Lots of info on those in the research papers on fasting and garbage disposal.

 

However , Valter Longo research concentrates on the efects of fasting on the effectiveness of

the cancer therapy with variety of medications including the TKI"s (such as D).

His research shows that fasting before start of the treatment rejuvenates the immune system

and gives superior results in comparison with the cancer therapy alone, without fasting.

He has published lots of papers covering this topic , but they deal with the cancer, not senescent

cells. However, many types of senescent cells show charcteristics of the cancer cells, just without

capacity for proliferation. So his research definitelly covers senescent cells , without saying

this explicitly.

Below there are two popular science articles on Valter Longo research: For more in depth research

google "Valter Longo Fasting":

 

"Fasting for three days can regenerate entire immune system, study finds"

 

http://www.telegraph...e-system-study/

"Fasting-like diet turns the immune system against cancer"

http://news.usc.edu/...against-cancer/

 

Personal Experience

When working with senolytics,(this including one 4 dose trial of "D+Q") I always water fast for at least

2 days before each dosing and then continue for at least 1 day afterwards. So far without major

complications beyond regular side effects as expected from the meds when taken alone. Therefore

from my experience adding fasting to senolytic therapy seems to be pretty safe. But then, my body

is pretty well adapted to fasting, which I have practiced for almost entire life ...(I am now in late 50"s).

Therefore can speak only for myself.

 

Do your own extensive due dilligence before you try it, please.

 

 

 

[DareDevil]

Hi sthira,

 

Thanks for talking about killing healthy cells. I thought both Dasatinib and Quercetin specifically targeted senescent cells and didn't attack healthy ones. That this might be the case definitely affects my take on dosage and frequency. I hope we can gain better insight into how they act in an organism with predominantly healthy cells in case of excessive dosage or frequency. Here is a "conclusive argument" in the Australian Lewis' Medical-Surgical Nursing: Assessment and Management of Clinical Problems. I am not sure how it qualifies here as a reference source, but they state about Dasatinib:

 

"this drug kills only cancer cells, leaving healthy cells alone"

 

https://books.google...XcoDDcQ6AEIHDAA

 

Regarding your other question, although I don't usually fast, I have nothing against it. Given the potency of D+Q I don't know if heightening their effectiveness through fasting is necessary. I would tend to think you'd need your body fully fueled to handle their onslaught because they have a fairly strong effect that feels like a full body blow. Others here who fast and also take D+Q, can they possibly tell us in what way their effect is different versus taking them with continued dietary intake?

 

My current supply of Dasatinib was sourced from True Life Science. While I didn't have it tested its effects seemed similar to the pharmaceutical Sprycel I tried a year ago. I am looking forward to receiving my Group Buy purchase so that I can compare its effects next time around. Meanwhile I am seeking other products to cycle while awaiting for future stacks of Epitalon and Dasatinib. Any suggestions are welcome. I am having trouble sourcing GDF-11 and Beta-Lapachone. If anyone here can recommend another good candidate with potent effects I would be very interested - thanks in advance !

 

Cheers,

 

DareDevil

Edited by DareDevil, 24 February 2017 - 09:50 AM.

[ambivalent]

If D is killing healty cells too, I'd have thought fasting would be highly important.

 

http://www.economist...ting-and-cancer

 

 

OT but hot off the press: fasting diet regenerates diabetic pancreas

 

 

Edited by ambivalent, 24 February 2017 - 01:11 PM.

[Nate-2004]

Wish I could fast like you guys but I could barely make it half a day without going insane, literally. My brain can't handle it and I can't function at all without food. Every time I've tried to fast it's been the most miserable thing I've ever put myself through, ever. You guys have a real tolerance for self-torture. Here's to hoping that not only do I get benefits from D+Q but that scientists find more and more fasting mimetics.

[Agent0023]

Josh Mittledorfs blog has mention of Valter Longo research and gives his commentary: http://joshmitteldor...ake-it-a-habit/

[ambivalent]

Nate,

 

Its's not torturous - take off and landing are the toughest parts of a fast. Mostly, to begin with, it is anxiety, once you realise there are no monsters, that hunger comes in waves, you relax and worry less. Detox symptoms are typically at their worst when starting out on fasting, but that it is a sign that the fast is needed. It is worth putting yourself through a few days fasting to at least make a judgement - almost everyone who fasts regularly wouldn't have imagined they could. The health benefits are so significant it is worth pushing yourself to see if you can adjust to it, rather than what we all initially tend to do, which is to falsely extrapolate our short term hunger experiences over the entirety of an imagined fast. XEva is worth chatting too/ reading up on (on the CR section, there really should be a fasting forum!)  - or head to the fasting connection / cure zone.

[Nate-2004]

Yeah what came in waves was sheer misery. I could not make it past 2pm without giving in because I needed to work and couldn't concentrate. My job as a computer engineer requires far too much brain power to pull off a day without food. Not sure how I would ever get over that awful feeling where I can't think and I'm incredibly irritable.

[ambivalent]

Generally, I'd say, there is no problem with productivity on day 1, once you're used to it.

 

I remember the guy from inhuman experiment did alternate day fasting for a year declare it was no longer an experiment but just simply he did. Perhaps 16-8 is the way for you, Mark Mattson insists that you're more productive, not less, when skipping breakfast. At times you experience exceptional alertness with longer fasts, but it fluctuates and is not ideal for work (I'd say).

 

Best to leave the subject now, we're off senescent cell clearance: there should be an 'off-topic thread' where you can take a fruitful but diverging conversation out of the current topic!

[Longevitarian]

Hi DD"

 

The D+Q does not kill healthy cells as long as you stick to the established protocols. Some people think

that when two medications are beneficial to the body when dosed separately and at the same time

harmless, then when taken together should actuall show benefit of both of them at the same time and

still be harmless. NOTHING MORE MISLEADING.

 

Modification of the medical protocol typically changes the way the medication works. In particular adding

new drug to existing one or change in dosing regime introduces uncertainty and unpredictability. Sometimes

it does not much difference, sometimes it improves the action of both drugs,sometimes it harms.

It is the years (or even decades ) of research and trials which are needed to establish which combination of

chemicals benefits, which is neutral and which harms.

 

Rebelling against that and doing stuff your own way its kind of suicidal. This is even more so when

dealing with synthetic chemical compounds to which no organism in existance and none in the past has

ever been exposed to, as it is the case of the most advanced cancer drugs.

 

Here I will use example of what you propose to do: specifically , adding betalapachone to the D+Q mix.

Will it be beneficial, neutral or harmful?

 

Lets see  what each of the therapies does:

D+Q WEAKENS cells to the point where the bad cell becomes suicidal or alternatively it is easy to

be killed by the cells of immune system.

 

What does the betaLapachone does?

It makes cells STRONGER via increase of the NADH-quinone

oxidoreductase 1 (NQO1) which in turn modulates cellular NAD+/NADH ratio in the end improving

parameters of the cells (by masking the damage). It is the case of both the good cells and bad

ones.It also marks up  the survivability of the cell (again the good ones and the bad)

 

Again, like with the (GH +D+Q) couple days ago mix of (D+Q+BetaLapachone) to me it is an example of

the SUCKING AND BLOWING at the same time.

 

Whether the mix benefits , harms or is neutral to health we will only know when you will take it and

survive to tell us about your experience.....He He He..

 

I would never do it myself.....though.

 

Sorry to disappoint again......I am such a party pooper..

 

Everybody is invited to counter me on above analysis.

 

[Valijon]

What about cycling between Dasatinib and Beta Lapachone? We wouldn't want to take many of these drugs continuously. Rapamycin comes to mind as a great example.

[Longevitarian]

Cycling might be good idea ...Removing bad cells with senolytics first and then keeping the good ones strong

and healthy with betaLapachone and other maintenance interventions until next cleanup.

[Izan]

in for 5 grams

[Rocket]

Hi DD"

 

The D+Q does not kill healthy cells as long as you stick to the established protocols. Some people think

that when two medications are beneficial to the body when dosed separately and at the same time

harmless, then when taken together should actuall show benefit of both of them at the same time and

still be harmless. NOTHING MORE MISLEADING.

 

Modification of the medical protocol typically changes the way the medication works. In particular adding

new drug to existing one or change in dosing regime introduces uncertainty and unpredictability. Sometimes

it does not much difference, sometimes it improves the action of both drugs,sometimes it harms.

It is the years (or even decades ) of research and trials which are needed to establish which combination of

chemicals benefits, which is neutral and which harms.

 

Rebelling against that and doing stuff your own way its kind of suicidal. This is even more so when

dealing with synthetic chemical compounds to which no organism in existance and none in the past has

ever been exposed to, as it is the case of the most advanced cancer drugs.

 

Here I will use example of what you propose to do: specifically , adding betalapachone to the D+Q mix.

Will it be beneficial, neutral or harmful?

 

Lets see  what each of the therapies does:

D+Q WEAKENS cells to the point where the bad cell becomes suicidal or alternatively it is easy to

be killed by the cells of immune system.

 

What does the betaLapachone does?

It makes cells STRONGER via increase of the NADH-quinone

oxidoreductase 1 (NQO1) which in turn modulates cellular NAD+/NADH ratio in the end improving

parameters of the cells (by masking the damage). It is the case of both the good cells and bad

ones.It also marks up  the survivability of the cell (again the good ones and the bad)

 

Again, like with the (GH +D+Q) couple days ago mix of (D+Q+BetaLapachone) to me it is an example of

the SUCKING AND BLOWING at the same time.

 

Whether the mix benefits , harms or is neutral to health we will only know when you will take it and

survive to tell us about your experience.....He He He..

 

I would never do it myself.....though.

 

Sorry to disappoint again......I am such a party pooper..

 

Everybody is invited to counter me on above analysis.

 

The only thing that sucks and blows at same time is your posts in this thread. What are your credentials? Where is your data?

 

All I hear is a lot of wild assumptions that are not rooted in experimental data. Any layperson can do bioscience by analogy and arrive at your baseless conclusions (or entirely different conclusions). Where is the data? Science without data is not science.

 

I wasn't aware that D+Q "weakens" all the cells in the body and only the weak senescent cells succumb and die. I guess that's why I feel so great since my 2 day cycles of D+Q.

Edited by Rocket, 25 February 2017 - 07:47 PM.

[Longevitarian]

Rocket

 

I am guily as charged, for not supplying the references....and alarmist postings.

There is no need to be emotional, though .....Here , below I am supplying

some scientific support to the previous statements.

 

Yes,D affects  all cells in the body , by downregulating of thevital biochemical

pathways ABL, the SRC family, and other tyrosine kinases over few hours

after dosing. Healthy cells typically do not mind that kind of intervention and

quickly recover after washout, while so called "addicted" to the pathways cells,

cannot survive downregulation and die.This is basic explanation of how D works.

Article below proves my point that both healthy and bad cells are affected by D.

 

"Centrosome aberrations and G₁ phase arrest after in vitro and in vivo

treatment with the SRC/ABL inhibitor dasatinib"

http://www.haematolo...ntent/93/8/1145

Background Dasatinib is a multitargeted inhibitor of ABL, the SRC family,

and other tyrosine kinases. We sought to evaluate the effects of this drug

on cell proliferation, centrosomes, mitotic spindles, and cell cycle progression

in vitro and in vivo.

Design and Methods Human dermal fibroblasts, Chinese hamster cells, human

osteosarcoma cells, and blood and bone marrow mononuclear cells from 32

patients with chronic myeloid leukemia, gastrointestinal stromal tumor, and

systemic mastocytosis as well as from six healthy individuals were investigated.

Results Dasatinib induced G₁ phase arrest in all cell lines and this was associated

with a decline in cyclin D1 levels.

Conclusions Dasatinib blocks the G₁/S transition and inhibits cell growth. It induces

centrosomal aberrations and a decrease of mitotic spindles. The effects suggest an

involvement of Src and ABL inhibition.

 

Now lets see what is the Src pathway. Google , to get Info about other pathways

mentioned in the article.

 

"Steroid Receptor Coactivator (SRC) Family: Masters Of Systems Biology"

https://www.ncbi.nlm...les/PMC2998129/

 

Are you getting where the SUCKING AND BLOWING at  the same time comes from when

using the mix of D+Q+GH comes from?!

The mix downregulates SRC by D and at the same time it tries to upregulate the same

SRC by steroids , which themselves are upregulated by GH. I am not even mentioning

other, possibly harmful effects inflicted by this combination....because I dont have time,

and nobody pays me for this work...So do your own analysis and post to the board...

please.

 

In the end we all want our lovable pet hamsters  be healthy and live happily ever after,

don"t we? 

 

 

 

 

 

 

[Longevitarian]

ERRATA TO MY PREVIOUS POSTING

 

I missed few lines of text when posting my previous posting: the missed part

follows the line:

 

"

Now lets see what is the Src (tyrosine kinase) pathway. Google , to get Info about

other pathways mentioned in the article."

 

"The Src family of protein tyrosine kinases (SFKs) plays key roles in regulating signal

transduction by a diverse set of cell surface receptors in the context of a variety of

cellular environments. SFKs have evolved many ingenious molecular strategies to

couple receptors with the cytoplasmic signaling machinery. The contributions to this

issue of ONCOGENE describe how this machinery regulates fundamental cellular

processes, including cell growth, differentiation, cell shape, migration and survival,

and specialized cell signals." -

ABOVE CITATION STATES VERY SERIOUS ROLE OF THE Src Tyrosine Kinase

WHICH IS OBVIOUSLY SOMETHING NOT TO MESS UP TOO MUCH (for example

by adding do the protocol  (D+Q) other medications.....

"Src family kinases, key regulators of signal transduction"

http://www.nature.co...l/1208160a.html

 

Following the leads, now lets explore specific interaction citing 

from the same article.

 

"CROSS-TALK BETWEEN STEROID RECEPTORS AND THE

c-Src-RTK"

"In recent years, evidence has emerged showing that both steroid hormones

and growth factors stimulate proliferation of steroid-dependent tumor cells.

Regulation of steroid receptors is well understood. These receptors are

ligand-activated transcription factors, which, upon ligand binding, dimerize,

recruit co-regulatory molecules and activate target gene transcription. As

described by Shupnick, response to steroid ligands can be functionally linked

to activation of Src or RTKs. Ligand-independent stimulation of steroid

receptor-mediated transcription by growth factors is now believed to occur

through activated protein kinases that phosphorylate the receptors and

co-regulatory proteins. Recently, steroid hormones themselves have been

shown to rapidly activate intracellular signaling cascades by virtue of their

binding to cognate cytoplasmic or membrane-associated receptors"

 

Finally we can cover the Family Of SRC ( do not mistake with the Src Tyrosine

Kinase) which are

 

"Steroid Receptor Coactivator (SRC) Family: Masters Of Systems Biology"

https://www.ncbi.nlm...les/PMC2998129/

 

 

 

 

 

 

 

 

[tintinet]

5 grams for round 2 also. Thanks!

[Rocket]

Another thing I am experiencing since my 2 day cycle of D+Q: my fingernails are really strong again. The backstory is that I'm not good about clipping my nails and once they get a certain length, which isn't long, they would chip or crack. That's a thing of the past. It's like I have 25yo fingernails again.  So far it's been a net positive experience except for the 1 day of feeling like I had the flu.

 

It will be good when other people start their experiments and what is reported.

Edited by Rocket, 01 March 2017 - 12:51 AM.

[sthira]

Another thing I am experiencing since my 2 day cycle of D+Q: my fingernails are really strong again. The backstory is that I'm not good about clipping my nails and once they get a certain length, which isn't long, they would chip or crack. That's a thing of the past. It's like I have 25yo fingernails again. So far it's been a net positive experience except for the 1 day of feeling like I had the flu.

It will be good when other people start their experiments and what is reported.

Taking biotin strengthens my finger and toe nails and makes them grow annoyingly fast. By any chance you're not taking more B vitamins are you?

[Logic]

Why don't ALL senescent cells die off,  immune sys upregulation and flu symptoms:

No-one here has asked the question: "Why dont all senescent cells die off as they should?  Why do some remain?"
Then the fact that D upregulates the immune system so potently AND is also an effective senescent cell killer also didn't seem to make much of a headline here..?

...Microbial infection can influence cellular functions that represent classical hallmarks of cancer, including stimulating proliferative growth, evading growth suppression, and preventing apoptosis, as well as emerging hallmarks, such as altered cellular energetics and avoidance of immune destruction...

...Viruses often overcome the inhibitory effects of DDR and the checkpoints that they have activated. This is seen for HPV, where the E6 and E7 oncoproteins that are the primary viral factors responsible for initiation and progression of cervical cancer contribute to many functions that combine to subvert cell-cycle checkpoints, induce genomic instability, and inhibit apoptosis...

https://www.ncbi.nlm...les/PMC4501477/

 

...Further dUTP incorporation into the genome of viruses may be a common mechanism that is used by infected cells to kill viruses or to undergo suicide [114]. Not surprisingly, many viruses encode their own dUTPase [114]. Once again the importance of these second messengers is highlighted by the observations that calcium binding proteins such as fortilin as well as the dUTP metabolizing enzyme dUTPase are capable of preventing cell death in response to some stresses when overexpressed in cells [111] and [113] (Khoury and Greenwood, unpublished)....

...The third well-studied class of cell survival proteins is the family of Inhibitors of Apoptosis (IAPs). These serve to bind and inhibit both initiator and effector caspases thus they can regulate both forms of apoptosis [153]. This functional class of protein was first described in the genome of baculovirus and underlines the resources placed by viruses in controlling apoptotic responses [154]....

http://www.sciencedi...167488910002764

 

In some cases, pro- or anti-apoptosis seemed to depend on the pathogenicity of the infecting strain. In human epithelial cells, asymptomatic carriage strains provoke the shedding of TNFR1 and prevent apoptosis

https://www.ncbi.nlm...les/PMC3463897/

Chlamydia pneumoniae infections prevent the programmed cell death on THP-1 cell line.

Chlamydia pneumoniae is an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in chronic inflammatory disease and atherosclerosis

https://www.ncbi.nlm...pubmed/12393203

 
In short; it would seem that senescent cells that refuse to die do so because pathogens, using them as a 'home base' from which to propagate make it so.
 
While we're at it; Its interesting to note the effect of Quercetin on the ...'incurable' common cold:
https://www.ncbi.nlm...les/PMC3360794/
(Yep; some research into the substances you plan to take IS worth it...!    )
Hmmm... what other pathogens does Quercetin affect..? 
https://www.google.c...teria pathogen

Now add in the upregulation of the immune system from D and it seems a waste not to do all you can get rid of free pathogens that may have been released either by cell necrosis or due to a genetic/signalling response to the destruction of their 'home bases'.

 

Lauric etc Acids, as found in Virgin Coconut Oil, and BHT disrupt the lipid layer on lipid coated virii like Flu, HSV, CMV, EBV, HIV, etc.  ie: All the scary ones you dont get shots for...
This lipid layer both disguises the virus against the immune system and allow it to dock wit and infect cells.

One problem:  BHT is going to cause Dasatinib to be cleared from your system 4-7 times faster (IIRC) than normal..!  

GoogleSiteSearch is in the Search dropdown menu at the top of the page!  

There are also a great many anti bacterials and ways to upregulate autophagy and marcrphagy mentioned here...

Of note is that Inositol, as found in most multis, downregulates autophagy

The biofilm disruptors mentioned by Psilociraptor1 who seems to have done a lot of research on the subject is also worth a look.

He mentions that only certain Stevia supps work.

http://www.longecity...ndpost&p=780907

 

NB that the 1st thing the immune system looks for when it finds a pathogen is vit D3, so it can kill it.

Also NB that the RDA of vit D3 has been underestimated by a factor of 10!

 

The flu like symptoms are more than likely a herxheimer reaction.

ie:  So much has died off in your system that your liver and kidneys etc are overwhelmed with junk to clear.

Adding anti pathogens and biofilm disruptors to the mix will add to the load.

So supps that help the liver and kidneys etc are worth a look, but may block the desired effect of D+Q.

New Members:

If you arent going to research these substances; at least take note of the various posters' post counts below their names.
I am at 2,573 posts and 467 ₮ points and am generally excused for not posting references etc by the older members who know my reputation.  Especially for old, previously referenced, searchable local posts.

(BTW:  Niner: 16,269 posts 3,494 ₮.  Maxwatt: 4,782 posts 1,504 ₮...)

 

(Upregulating apoptosis):
Caspases (cysteine-dependent aspartic acid specific proteases) are central to the process of apoptosis.
https://www.ncbi.nlm...les/PMC3463897/

Edited by Logic, 01 March 2017 - 01:10 AM.

[Logic]

Navaticoc;ax /ABT-263:

 

...effectively depleted senescent cells, including senescent "stem cells" of the bone marrow and muscle. Depletion of the senescent cells appeared to reduce premature aging of the bone marrow caused by irradiation, and even rejuvenated the function of stem cells in normally aged mice. "Our results demonstrate that clearance of senescent cells by a pharmacological agent is beneficial in part by rejuvenating aged tissue stem cells. Because a decline in tissue stem cell function is associated with exposure to radiation and aging, we believe clearing senescent cells and rejuvenation of tissue stem cells could have a major impact on mitigation of radiation injury and treatment of diseases of aging...

http://www.longecity...cells-in-aging/

 

...Navitoclax can be purchased, and dosages can be established from the human cancer studies and the senescent cell clearance rodent studies (there is a fairly standard method of going from mouse or rat dosage to human dosage). There is comprehensive human safety and side-effect data to look at, but only rodent data for its effects on senescent cells...
http://www.longecity...ember-7th-2016/

 

Moreover, at 25 days, which can be considered a very advanced age for a worm, the percentage of ced-9(n1050) survivals was more than double compared to wildtype.

http://www.longecity...nce-and-bcl-xl/

 

The main side effect seems to be Thrombocytopenia:

https://en.wikipedia...wiki/Navitoclax

This should not be an issue  with intermittent dosing..?

 

I am going to see if I can get this!?

 

[jmorris]

The main side effect seems to be Thrombocytopenia:

https://en.wikipedia...wiki/Navitoclax

This should not be an issue  with intermittent dosing..?

 

I am going to see if I can get this!?

 

In many ways, Navitoclax is superior to Dasatinib as a senolytic.

 

It works by inhibiting members of the BCL-2 family which, in turn, block the pro-apoptotic proteins Bax and Bak. When Bax and Bak are present and not inhibited, they promote permeabilization of the mitochondrial membrane and the release of cytochome C. This starts off the apoptotic cascade. 

 

The BCL-2 family of anti-apoptotic proteins includes: BCL-2, BCL-XL, BCL-W, MCL-1, and BFL-1/A1.  There are many cells in the body that are kept alive by the presence of the proteins listed above. Inhibiting them in the body leads to the following on-target effects:

 

BCL-2: Lymphopenia

BCL-XL: Thrombocytopenia

BCL-W: Sertoli cell death and eventual testicular degeneration. Nociceptor axonal neuropathy.

 

Navitoclax inhibits all three of these. Like Rapamycin, it affects the gonads. Unlike Rapamycin, we don't have any data about recovery in humans. I would jump at the chance to get my  hands on some Navitoclax but the Sertoli cell death makes me worry.

 

Proof of concept with ABT-737 (non-orally available version of navitoclax) inhibiting BCL-W and BCL-XL:

https://www.ncbi.nlm...les/PMC4823827/

 

First paper showing Navitoclax is senolytic:

https://www.ncbi.nlm...les/PMC4854923/

 

BCL-W linked to Sertoli cell survival:

http://www.pnas.org/...5/21/12424.full

 

Testicular degeneration after Navitoclax treatment:

http://ar.iiarjourna...g&pmid=24982396

 

"Dose-dependent testicular toxicity was observed in both rats and dogs. After 4 weeks of once daily dosing, the NOAEL was 3 mg/kg/day in the rat, with less severe effects at the end of a 4-week recovery period suggestive of reversibility, and 1 mg/kg/day in the dog, with minimal, non-adverse effects at the end of a 4- week recovery period. There was no evidence of reversibility with 13 weeks of dosing and a 13-week recovery period. "

 

As far as I can see, no incidence of neuropathy has been found yet in people taking Navitoclax. Here is the reference about BCL-W if you are curious:

https://www.ncbi.nlm...les/PMC3074348/

Edited by jmorris, 01 March 2017 - 02:48 AM.

[Vantika]

I recently became interested in Navitoclax myself, with cost and sourcing being the main hurdles to obtaining it.

 

I would definitely be interested in a group buy, Logic, if you're up for organizing one.

 

[jmorris]

"Dose-dependent testicular toxicity was observed in both rats and dogs. After 4 weeks of once daily dosing, the NOAEL was 3 mg/kg/day in the rat, with less severe effects at the end of a 4-week recovery period suggestive of reversibility, and 1 mg/kg/day in the dog, with minimal, non-adverse effects at the end of a 4- week recovery period. There was no evidence of reversibility with 13 weeks of dosing and a 13-week recovery period. "

 

 

In men, Navitoclax testicular toxicity could be monitored pretty easily with a cheap microscope and a hemacytometer (sperm count), and/or testosterone testing in between intermittent doses.

[Longevitarian]

Hi Jimmoris'

 

Being castrated by the Navitoclax may give additional lifespan and healthspan gains.

Studies on eunuchs show up to 20 years life expectancy gains in comparison with

fully endowed dudes. Here is an article:

Effects of Castration on the Life Expectancy of Contemporary Men

http://lesswrong.com..._expectancy_of/

 

For anybody , who decides to go all the way with Navitoclax .....don"t blame

me for pointing to that unquestionable opportunity, if you decide it wasn"t such

a good idea afterall.... I am only a messenger.....

 

[Longevitarian]

Below I include study involving HEALTHY volunteers. This is what

would be of primary interest for us. Since I presume each of us

will be giving it to their HEALTHY Chinese Hamster.....and we do

not want our hamsters to suffer any major side effects or turn into

pigeon.....or worse .....into frog.....

 

."Two relative bioavailability/food effect

       studies with either a 25 mg dose or 50 and 100 mg doses of

          navitoclax were conducted sequentially in healthy female

   volunteers of non-childbearing potential.

   Results/Conclusion:

     Navitoclax was well-tolerated in both studies in healthy

           volunteers, and did not impose risks beyond the minimal

       levels expected in healthy volunteer studies. Compared to a

         similar study in cancer patients, the studies in healthy

       volunteers generated higher quality data in a short period of

   time to support formulation selection"

 

     "Studying Navitoclax, a Targeted Anticancer Drug, in Healthy

     Volunteers – Ethical Considerations and Risk/Benefit

Assessments and Management"

 

http://ar.iiarjourna...7/3739.full.pdf

 

[DareDevil]

Hi Longevitarian,

 

No, we won't blame you for our trials, nor shall thank you for any successes you might discourage by posts that invariably seem to turn to doom and brimstone. The latest encouraging us to actively seek out chemical castration to fend off aging is revealing of an attitude of fear-mongering present in a number of your posts here. It seems beyond mere caution, more to the point of inciting us to not experiment at all? Unless there is a zero risk factor or it is unanimously supported by the entire bought and paid for pharmaceutical community?

 

In this forum it is common knowledge that much of the pseudoscientific data produced by studies is engineered to deliver pre-established results for a variety of motives. Hence one study claiming something isn't relevant alone and one may also question the source, those most established often being the least reliable due to economic ties to interested parties. Far fewer of these are genuinely neutral pure research oriented experiments.

 

So it should come as no surprise to you that I beg to disagree with a barrage of "don't say you weren't warned" admonishments, given that I'm quite contrary in spirit, a daring experimenter, nicknamed DareDevil.

 

At times I wonder if you're aware of the experimental character of this community when you post? Am I incorrect in stating that most Longecity members seek to individually understand and decide for themselves? Whether or not to expose their lab rat to substances that might help cure their ailments? Ailments that large industrial interests fail to cure or might even have a vested economic interest in perpetuating? Others here seek to improve their immune system. Or to combat the ravages of aging. And while some substances can be broadly tested in lab or in vivo, be proven safe with known side-effects, others may not. It is the nature of the quest.

 

Many members sharing information in this forum seek to determine for themselves what constitutes an acceptable risk/benefit ratio. While we may caution one another on obvious eminent risks, naturally, few insist on zero risk or cry "wolf" at every shadow in the woods. For this risk adverse mindset, there is a large pharmacological community you can join, by making an appointement with your family doctor and going to your local pharmacy. This is hardly the place.

 

We are here because that very same medical and pharmaceutical establishment has to our mind failed to sufficiently address issues we find important to the full extent of their potential. Their failings have prompted the need for Longecity members to explore for ourselves, at our own risks and perils, new avenues of treatment and prevention.

 

Big Pharma may have very different motives from ours, which might preclude life extension?

 

At minute 16'30" we see how they may view our immunity and anti-aging quest as a problem:

 

DareDevil

[DareDevil]

I recently became interested in Navitoclax myself, with cost and sourcing being the main hurdles to obtaining it.

 

I would definitely be interested in a group buy, Logic, if you're up for organizing one.

 

Hi Vantika,

 

Unless a few brave home labs take the initiative others will never know if this is a viable path to life extension. So if there's a group buy, tell Logic I'd be on board. My doctor regularly monitors my Testosterone levels so I can adjust or stop intake should they plummet. Of course I'd report back, as this is how we gather informal bro-science (and sis-science) feedback on the curative or rejuvenating potential of tested substances.

 

Cheers,

 

DareDevil

[Longevitarian]

My previous post included article which has been already posted by

jmorris. My apology for my inadvertence....

 

However, following article is absolutely astonishing........

 

"Clearance of Senescent Cells By ABT263 Rejuvenates Aged

Hematopoietic Stem Cells In Mice"

 

http://www.nature.co...ll/nm.4010.html

 

Above study might indicate that Navitoclax is breaking major barrier to life

extension, which is exhaustion of the hematopietic stem cells. As it was the

case of a 115 years old lady who died quite healthy .....The cause of her

death was established that only two (2) hemopoietic stem cells worked to

replenish all her blood....not enough to sustain her life.....

New Scientist article follows.....

 

"Blood Of The Oldest Woman Hints At Limits Of Life"

https://www.newscien...limits-of-life/

 

 

[Longevitarian]

DD"

 

The "chemical castration" was kind of educatational joke, directed at nobody....

no need to get upset.

 

As to the population growth, this dude talking about exponential growth , and

its dangers is a bit underinformed. He does not cover latest projections of

world population growth. Below is the graph, which clearly shows a slowdown.....

Some of the countries such as most of Europe ....Russia , Japan already have

negative population growth which they try to compensate with aggresive

immigration policies. Sometimes TOO AGRESSIVE as it is the case of latest

developments with refuges in Europe.

 

http://www.mhhe.com/.../ppt/sld003.htm

 

My alarmist postings reflect my attitude with respect to any experiments involving

chemicals. And this is : SAFETY FIRST.

[TaiChiKid]

It is interesting to note the dual affinity of Q to the hemagluttin (HA) coat.  Thank you for sharing, Logic.

 

Some of the flu like symptoms people are experiencing come from interferon from Thelper cells as the cells express surface antigen protein fragments.

 

In the case of the D&Q protocol, I assumed that the combination had a dual role in fighting cancer:  activating cytotoxic cells, as well as helpers.

 

Incidentally, there is a type of highly absorbable quercitin called Querciting EMIQ which is 18x more absorbable and thus bioavailable than quercitin.  Assuming the rate of 1 part D to 10 parts Q, a single 50mg tablet of Q EMIQ would be sufficient to obatin the 1:10 ratio.

Edited by TaiChiKid, 01 March 2017 - 09:21 PM.