731 replies to this topic

[Longevitarian]

Just to add explanation to my previous posting: Vitamin D is neccessary for apoptosis

to be executed. No Vitamin D No Apoptosis of your senescent cells. This is why people

with low Vit D get more cancer.

[jmorris]

I just found this human clinical trial using dasatinib and quercetin . I guess they think that quercetin is promising enough in humans to use it in a trial, which is reassuring.

The dosage is dasatinib 100 mg and quercetin 1000 mg for 3 consecutive days.

https://clinicaltria...enolytic&rank=1

 

When I started graduate school almost twenty years ago one of the things I remember most was journal club. In journal club, us green Ph.D. students would sit with a wise professor for an hour and hear them dissect and lambaste paper after paper. This was a valuable process. It took years of this and many years further of running my own failed experiments for me to really understand what I now know was the central point of the process. Graduate school was not about learning how to run experiments. Nope. Nor was it to learn the names of 30 enzyme pathways or 5,000 proteins. Rather, it was about learning how to be skeptical. That is what truly separated us graduate students from the professors who were teaching us. "It is the illusion of knowledge that is the obstacle to discovery." Try saying that a few times. Let it sink in. Just because you want something to be true does not make it so. In fact, due to bias it makes it less likely. That's a concept that is exceedingly hard to grok for most people. And just because something is written in a paper, that does not mean it is true. You have to educate yourself and read very, very carefully. In fact, a large proportion of papers should never have been approved by reviewers in the first place. 

 

But how can you tell? You need to look at many things:

 

First and foremost, start with the assumption that everything you are going to read is wrong.

 

Next, In what journal is the paper published? (Some journals have good reviewers and some are rubber stamps. As much as I hate the idea of the journal "impact factor", it does help to separate the wheat from the chaff.)

 

Who wrote the paper? What is their background? Are they a Ph.D. or an M.D. or an M.D. PH.D? (I know this sounds ad hominem but MD's typically have a shallow understanding of the science behind things and are (perversely) good at getting funding. I think that's why "The Lancet" exists, to give them someplace to save face after being rejected from Nature, Science and Cell.)

 

What is the evidence they give? Here's a tip: If you are short on time, don't bother reading the results section, instead look first at the tables and figures. With practice, you can save yourself a lot of time in invalidating a paper. (I learned this trick from one of my old professors.)

 

If the paper still looks good, what are the specific methods? Are there any limitations to their techniques? (This is going to be hard for those of you who have never worked in a lab but it's really a worthwhile endeavor. Look up the methods in wikipedia.)

 

How do they statistically treat the data? There are many ways to "cook" data to make it look better, some more obvious than others.

 

But what we have here is not even a paper. An MD at Mayo Clinic has gotten funding from someplace to run a trial.

 

No data. No statistical methods. No evidence whatsoever.

 

So in this case the level of evidence is not even zero. They have not gotten to the evidence part yet. So while you may find it reassuring that this trial exists, in the immortal words of Wolfgang Pauli: "It's not even wrong." 

 

I hope you all understand that I don't get any prize from being right. Quite the contrary, arguing against a commonly held belief is going to do nothing but make people not like me. In 99% of situations, in spite of having knowledge that contradicts others I just keep my mouth shut. Because, who cares, right? If someone thinks that vitamin C is going to make them live forever, awesome. One more happy person on earth.

 

But as little as I know you all, I still feel a certain level of belonging here. We all share the same irrational, quixotic goal. I have the advantage of having spent my life in science but most of you (presumably) don't. It's my duty as a scientist to spread knowledge. Watching you all share what I believe is a false hope makes me sad. Hence, my decision to speak up. (It is also distracting you all from moving on to the next most promising thing, likely navitoclax or something like it.)

 

This will likely be the last I write or speak of this subject. If you all want to take quercetin orally, that's cool with me. I wish you the best. I can sleep soundly knowing I have done my best to quash this bit of well-meaning misinformation.

 

FWIW, I have contacted Dr. Hickson and inquired into her logic behind the dosing in this trial. If she tells me some information that invalidates this position, even just a bit or even just in kidneys I'll happily post it here immediately.

[Andey]

 

 

 

 

   Well writtten, sir.

   You should understand though that community here is leaning heavily towards self experimentation even without any scientific data before hand, just chasing hopes. )  And this community could benefit greatly from man like you.

   Thought I dont think that even poorly designed study (and tiny in vivo studies almost impossible to design well) would do more harm than good. Probably its just a pilot cowboy style to see if there any prominent and undeniable effect from administration to justify more expensive one further down the road.

[ambivalent]

Hi Jmorris,

 

All of us, to some extent or another are not indifferent between switching to a new belief when we are invested in an alternative (especially scientists); however, this resistance operates at different levels in people from an unconscious response to over-weight some supporting anectdote or simply fail to vigorously pursue the merits of a counter line of inquiry, to one of blind faith bent on rejecting anything disconfirming evidence. Personally, I don't believe there would be some mindless rejection, partiularly on this thread, to evidence batting quercitin out of the park but (I would say) there might be some irritation if the suggestion is hinted at from the outset is that people here are not mature or intellectually flexible enough not shoot the messenger when uncomfortable, debunking evidence is presented. If the person is not aware of this presumptive tone when presenting an argument, it might be very easy to mistake hints of antagonism to be resultant from a fear of unshackling our chains and heading out the of the shadows of Plato's cave. 

 

Your knowledge will be welcomed and of enormous value, I am quite sure. On this forum we are all a mixture of lab-rat and lab-coat, some of us are far furrier than others count myself amongst the furriest - so not having tried any senolytic (save some modest amount quercetin) yet, I look forward to your contributions.

 

Regarding, critiquing published papers, it would be of very great service, to provide perhaps several examples of how deploying the thought processes you've articulated would have led you to reject conclusions many of us would have accepted at first glance.     

 

Thanks again for your research.

 

 

[Iuvenale]

Thanks, jmorris, for your wise comment. I am not taking an experimental proposal as proof on the bioavailability of quercetin, but only as a source to nudge the needle of uncertainty more to thinking that it might be. After your original post, it seemed futile to take it at all, but now it seems possible that it might help. And, if it doesn't, it probably won't hurt.

As for our desperate scrambles for hope, I'm guilty as charged, as are most of the people here. However, there is also an excitement at being the first to try something that is possibly transformative. Yes, it's stupid and crazy at some level. I'm on day two of three of D+Q and watching nervously for symptoms of excessive bleeding, liver failure, etc. when I could just wait a few years for researchers to do this as an experiment or come up with a safer senolytic. But, hey, everyone needs a hobby.

Please post often. The thoughts of a real medical researcher are what's needed here.

[Valijon]

Some really good points brought up here. Especially by jmorris. In college I was taught to question everything. Some people didn't receive these same benefits or develop critical thinking skills. I believe this is exactly what jmorris is looking to explain. I always subscribe to the idea of liars figure and figures lie when reading something.

We should all beware of sketchy sources and anything at all from a supplement company.

[Longevitarian]

Hi Jmorris"

 

I sympathise with your scepticism, but frankly say I am very curious with what kind

science will they come up with the D+Q human trial. Yes, they are cutting the corners

from the point of view medical research protocols , but not too much.

If the trial will proceed , they will likely get all the data confirming or rejecting the

applicabilty of the senolytic action of D+Q from rodents to humans, which is great.

On top of this if they get indications senolytic action in the kidney or perhaps other

organs it will be revolutionary......

We should be supportive of this kind of initiative ......it will benefit all of us....

 

my $0.02

[mikey]

As to blood pressure, mine came down, maybe 10-20 points for both systolic and diastolic a week or so after the second of my D&Q exposures.

 

However, after a couple weeks on a stressful day it measured at 150/90, so I took a med.

 

It has been considerably lower than it was before D&Q, however it doesn't seem to be staying as low as it did at first.

 

Do I need to do another one day of D&Q 50mg+50mg five hours later or ????    

[slotrite]

This looks promising for my achy joints; http://www.medicalne...cles/317185.php

[Longevitarian]

Hi Slorite

 

The senolytic medication UBX0101 they mention in the article is either Navitoclax itself

or close derivative of Nav....

[Longevitarian]

Below is one example of extensive research on why Vitamin D should

be considered as an accompanying element of every cancer therapy.

While it does not cover the senescent cells ablation explicitly it the

research easily extends to the senolytics as well.

 

MECHANISTIC EFFECTS OF VITAMIN D ANTICANCER EFFECTS

http://www.sciencedi...083672915000679

 

The article is in support of my previous postings which propose

that D+Q+F should be supplemented vith vitamin D. This is what I

have done in my original experiment.

[Longevitarian]

Here Is Another One:

 

Apoptosis Induced by Vitamin D Compounds in Breast Cancer Cells Is Inhibited by Bcl-2 but Does Not Involve Known Caspases or p53

 

http://cancerres.aac...tent/59/19/4848

[LOOKINGFORTIME]

Sorry could not get label smaller. Would this be a good form of Quercitrin?

 

 

 

[Iuvenale]

I just finished three days of D+Q. First day was 40 mg D and 800 mg Q (Swanson's https://www.swansonv...g-30-veg-caps).Second day was 60 mg D and 1600 Q. Third day was 40 mg D and 800 Q. I used a 10 mg scoop to measure the dasatinib so it may not have been completely accurate. I discontinued my huge number of supplements a week before and after the experiment to avoid excessive bleeding and protection of the senescent cells.

 

Side effects were yellow feces for one day (after googling, I found that this could be liver problems or fat in the feces, possibly from fat cells being destroyed), tingling in feet and hands, intermittent sharp painful sensations in skin. I don't feel any increase in energy or wellbeing, but there may be a recovery period while blood cells etc. regenerate. 

 

Does anybody else have reports to share? I would think that others would have tried it by now.

[Andey]

I just finished three days of D+Q. First day was 40 mg D and 800 mg Q (Swanson's https://www.swansonv...g-30-veg-caps).Second day was 60 mg D and 1600 Q. Third day was 40 mg D and 800 Q. I used a 10 mg scoop to measure the dasatinib so it may not have been completely accurate. I discontinued my huge number of supplements a week before and after the experiment to avoid excessive bleeding and protection of the senescent cells.

 

Side effects were yellow feces for one day (after googling, I found that this could be liver problems or fat in the feces, possibly from fat cells being destroyed), tingling in feet and hands, intermittent sharp painful sensations in skin. I don't feel any increase in energy or wellbeing, but there may be a recovery period while blood cells etc. regenerate. 

 

Does anybody else have reports to share? I would think that others would have tried it by now.

 

  Transient yellow feces could be anything starting from the color of quercetin itself, and most probably just faster transit time through digestive system so bilirubin dont get converted into darker color. If its were me I would not be bothered much with it.

  Tingling etc could be some nerve damage going on, could be from over activation of immune system or something else.

Dasatinib is a far cry from OTC drug, it have very thick manual full of side effects. Be careful and stay on the safer side )

[SearchingForAnswers]

Hmmm, I was just thinking.

 

I've been preloading on Quercetin in order to start the D+Q+F therapy starting this Friday. However, I just completed the Rezum prostate reduction therapy two weeks ago. I'll be peeing blood for a number of weeks now.

 

Would this be a contraindication and should I wait longer?

[Nate-2004]

You did see the posts above by jmorris on the bioavailability of Q right? 

[SearchingForAnswers]

Yes,

But not being a biochemist I don't know if there is some other mechanism by which it works. I believe he's correct, but hey I've got it anyways and I don't think it'll do any harm.

[Longevitarian]

Searching For Answers!

 

If any part of you is healing , I would avoid any major intervention

with medications , especially those which induce apoptosis ......

its extremely risky ........

[Heisok]

https://youtu.be/adg3vUez3EU?t=1053 "Judith Campisi, Ph.D. on Cellular Senescence, Mitochondrial Dysfunction, Cancer & Aging "

 

You need senescent cells to heal some wounds. In the Found My Fitness video at around where the link will take you. Dr. Campisi specifically warns about treating before surgery. Earlier in the video, she mentioned skin healing needs senescent cells, if I heard correctly.

Also, Dr. Patrick puts links in the first pinned comment to the video. They take you to different sections.

 

 

Hmmm, I was just thinking.

 

I've been preloading on Quercetin in order to start the D+Q+F therapy starting this Friday. However, I just completed the Rezum prostate reduction therapy two weeks ago. I'll be peeing blood for a number of weeks now.

 

Would this be a contraindication and should I wait longer?

 

Edited by Heisok, 02 May 2017 - 12:32 AM.

[Rocket]

If the body needs senescent cells for wound healing, how do the very young without accumulated senescent cells heal these injuries? I've heard this parroted about this website.

[Heisok]

If the body needs senescent cells for wound healing, how do the very young without accumulated senescent cells heal these injuries? I've heard this parroted about this website.

 

Good point, sorry that I did not accurately quote the Dr. Campisi. They can be beneficial for wound healing, and tissue repair through apparantly multiple factors. I inaccurately used "needs".

 

 

 

 

 

Edited by Heisok, 02 May 2017 - 03:02 AM.

[Alpharius]

If the body needs senescent cells for wound healing, how do the very young without accumulated senescent cells heal these injuries? I've heard this parroted about this website.

Senescent cells can be caused by the injury so they are automatically there where wound healing is needed. The secreted factors from the senescent cells are important for the regeneration because they aid the stem cells and add to their "stemness", but the same factors can act as oncogenes: Means either senescent cells cause cancer if they are overactive or the nearby cells become senescent too (oncogene induced senescence). 
 

[DareDevil]

So if someone undergoes systemic stem cell rejuvenation, they won't want to kill senescent cells first?

[SearchingForAnswers]

Well, I am abut 38 hours into my fast. I'm not sure if Longevatarian broke his fast at 48 hours and then took the dasatanib & micelle querecetin (courtesy revgenetics), or how he did it. I think I'll take it tomorrow after work and break the fast shortly after. Unless I should take it with food?

 

Suggestions appreciated.

[Andey]

Well, I am abut 38 hours into my fast. I'm not sure if Longevatarian broke his fast at 48 hours and then took the dasatanib & micelle querecetin (courtesy revgenetics), or how he did it. I think I'll take it tomorrow after work and break the fast shortly after. Unless I should take it with food?

 

Suggestions appreciated.

 

  Quercetin is lipophillic. It could help a lot if you mix it beforehand with some fat. Fast mimicking diet by dr Valter Longo is based on fat so it should be ok. Now I always fast with some MCT Oil, counterintuitevely it makes fast harder though.

  My guess is that in the end of the day fast is not really needed for Q+D.

  Dasatinib effective bioavailability is also better (by 16% accordingly to some study) if its taken with meal, but its easier to manage its dosage directly without interactions. Only exception is if you take PPI as it absorption could be impaired by low acidity in stomach (this is from its manual, its better to read it to know all interactions).

[Nate-2004]

Nope, regardless of its absorption, orally it still goes through the liver and converts to the wrong type of Q. 

 

I plan to try the DMSO topical and sublingual administration sometime soon. I also considered the possibility of putting some on the thinner portions of my scalp. I know the going theory is that gray hair is related to senescent cells affecting the catalase that breaks down hydrogen peroxide and may also affect hair thinning with age. Perhaps clearing those cells would help not only to undo grey hair but thicken it as well.  Only worry is that topically, Q may turn my hair yellow at first haha.

 

I still have yet to find any comprehensive, detailed understanding of the whole mechanism for why hair thins or greys. You'd think this would be understood by now. I mean, the cosmetic industry is always booming.

Edited by Nate-2004, 04 May 2017 - 07:09 PM.

[Longevitarian]

Hi SearchingForAnswers

 

I was continuing fasting for another 6 hours after dosing . During that time

I was sitting and watching videos while observing closely and recording all

symptoms as they were showing up. To pick up even tiniest effects of the 

medication It is important that you are in very stable environment.

Typically in clinical studies people are required to sit in upright position for

at least first 4 hours after dosing....I would recommend that you stay at home

for 24 hours after dosing .....

 

[Iuvenale]

I got shingles from this protocol. I've never gotten it before.

 

Waiting patiently for it to pass and hoping I don't get post-herpetic neuralgia. Taking lemon balm, beta glucans, and lactoferrin.

 

I guess we need those white blood cells after all. 

[sthira]

I got shingles from this protocol. I've never gotten it before.

Waiting patiently for it to pass and hoping I don't get post-herpetic neuralgia. Taking lemon balm, beta glucans, and lactoferrin.

I guess we need those white blood cells after all.

That's interesting. Were you diagnosed with shingles?