731 replies to this topic

[Rocket]

Ok, so for the non cellular biologist, dasatinib eliminates senescent fat progenitor cells. Of what benefit is that to other tissues like skin and muscle and internal organs?

[jmorris]

Ok, so for the non cellular biologist, dasatinib eliminates senescent fat progenitor cells. Of what benefit is that to other tissues like skin and muscle and internal organs?

 

When cells are sick or under stress, they release chemical messengers called cytokines. These cytokines are meant to alert the immune system that an invader is present or that the sick or cancerous cell should be removed due to dysfunction. When cells become senescent, this process goes haywire. The cells release signals that induce both local and distant cells to enter an inflammatory state, sometimes even inducing other healthy cells to become senescent as well in a kind of chain reaction. This mix of inflammatory cytokines is called SASP, the Senescence Associated Secretory Phenotype.

 

Recent thinking is that SASP causes organism-wide inflammation and that this inflammation is the primarily cause of the frailty seen in aging. This is why people are calling it "Inflamm-Aging".

 

So even though Dasatinib only helps to eliminate senescent fat cell progenitors, these cells have a negative influence beyond just the local environment in which they are found. 

 

Will elimination of just fat cell progenitors be worth the risk of taking a leukemia drug with potentially serious side effects? The truth is that we just don't know. Hopefully, these side effects can be avoided by using Dasatinib intermittently.

Edited by jmorris, 26 December 2016 - 08:48 PM.

[niner]

I don't know if Dasatinib acts only on fat cells.  Of the cells that they looked at, it was presumably better with senescent fat cells, but given the conserved mechanisms of apoptosis, it seems unlikely that the particular kinase that Dasatinib hits would only exist in fat cells and no where else.  I would expect it to have at least some ability to take out other types of senescent cells as well.

[Rocket]

I don't know if Dasatinib acts only on fat cells. Of the cells that they looked at, it was presumably better with senescent fat cells, but given the conserved mechanisms of apoptosis, it seems unlikely that the particular kinase that Dasatinib hits would only exist in fat cells and no where else. I would expect it to have at least some ability to take out other types of senescent cells as well.

So not a silver bullet against all senescent cells in all tissues, like that mouse study where they were bred to have their s.cells obliterated with the drug that targeted and killed their s.cells?

I see TLR is selling some concoction of Dasatinib and quecertin. Does anyone know anything about what they are selling. Is it the real deal Dasatinib?

[Valijon]

Who is TLR?

[Rocket]

Who is TLR?

 

Team TLR (true life research I think). There is a thread in the supplements section about them.

[Valijon]

I'll check it out thanks!

[Iuvenale]

5 grams for me.

[sthira]

10 grams, thanks.

[Nate-2004]

I haven't heard much on this since the new year but have you guys read this?

 

http://joshmitteldor...-they-kill-you/

 

Neither quercetin nor dasatanib appear all that promising. 

 

http://joshmitteldor...scoveries-ever/

 

 Though they prove the principle, they don’t distinguish senescent cells efficiently enough to offer an attractive therapy.

[Valijon]

Maybe we should have gone for a Rapamycin group buy instead?

[jmorris]

Maybe we should have gone for a Rapamycin group buy instead?

 

If you are man past your reproductive lifespan and don't mind your testicles degenerating and then having to start TRT then yeah, Rapamycin might be a good idea.

 

I don't fit into that category (yet) so Dasatinib it will have to be until something better comes up.

[Valijon]

Are we talking testicular atrophy or something even more severe? Can you link me to this information please?

[jmorris]

Are we talking testicular atrophy or something even more severe? Can you link me to this information please?

 

It's atrophy but not exactly the kind you get from low LH and FSH. For a good review, check out the discussion in this paper:  

 

https://www.research..._But_Reversible

 

Sci-hub: http://www.sci-hub.i...b013e31824bf1f0

 

It's a study in mice that suggests that the changes are, to a large extent, reversible. This is backed up by data from kidney transplant patients. 

 

So, on one hand we have a study showing some pretty miraculous life-span effects of Rapamycin in mice. On the other hand, we know that there is reproductive toxicity. Rapamycin's biggest problem in my mind is that we have no idea how much and how long is needed. The mice were treated for three months. What does that mean for humans? Does it mean that humans have to be dosed for three months as well? Or does it mean that the time must be adjusted for our increased lifespan? That would be 7-8 years. How long does the effect last? In mice it only needed to last until the end of their (still) short lives.

 

It's fun to try to extrapolate these things from an animal studies. But without more studies in primates, there is really no way to know.

 

I'd still like to have another child or two in the next few years so the risk/reward for this has me torn. In a few years I'll probably change my tune. If I had the chance to stash some Rapamycin for later I might do that as well.

[niner]

I haven't heard much on this since the new year but have you guys read this?
 
(Mitteldorf stuff)

Read it, not impressed. The guy's not a biologist, gets a lot of things wrong.

[Nate-2004]

 

I haven't heard much on this since the new year but have you guys read this?
 
(Mitteldorf stuff)

Read it, not impressed. The guy's not a biologist, gets a lot of things wrong.

 

 

What did he get wrong about Dasatinib?

[Valijon]

Yes, this is a bit off topic and I'll move anything further to a Rapamycin thread. I'd say its a good idea to stash anyting that might turn out to be effective. That includes some dasatanib and some Rapamycin. Anything thats proven effective and even moderately safe is going to explode in demand and price.


Thanks for the information related to the atrophy with Rapamycin. I'm still looking forward to trying some dasatanib.

[Logic]

All the best for the new year to everyone.

I have had a 'jol' over the festive season and hope the same is true for you.

 

I am going through the latest D related Emails and PMs and will post a redacted copy here before sending out costings.

 

 

 

 

[Logic]

Guys please give me your postal address if you want in on the buy.
You might also supply a phone #, should you be out when USPS delivers.
Email address as an alternate means of comms is also up to you.

 

[Logic]

Making the minimum order five grams everyone.

Aliquoting and postage will be a nightmare as is. 

Hope that is OK with everyone.

[Nate-2004]

Making the minimum order five grams everyone.

Aliquoting and postage will be a nightmare as is. 

Hope that is OK with everyone.

 

That's fine, I'm still good with 10 and you already have my info.

[Valijon]

5 hmm....I don't know. How many grams have we all committed to? Whats our final price for a 5 gram minimum?

[maxwatt]

For those interested in senolytics such as dasatinib, I'd like to call your attention to this post  http://www.longecity...ndpost&p=801755    

which links to a crowdfunding site for Cellage, a company seeking to develop molecules more specifically targeted to specific senescent cells, not just those that this happens to reach, perhaps with an overly broad sweep.

[Nate-2004]

For those interested in senolytics such as dasatinib, I'd like to call your attention to this post  http://www.longecity...ndpost&p=801755    

which links to a crowdfunding site for Cellage, a company seeking to develop molecules more specifically targeted to specific senescent cells, not just those that this happens to reach, perhaps with an overly broad sweep.

 

As far as I have understood it, quercetin and dasatanib both target specific senescent cells, the former being endothelial and the latter being certain kinds of fat cells.  

 

I'd love to help crowdfund senolytics though. Thanks for the link.

 

 

Logic what is the status on the group buy?

[DareDevil]

FYI in my initial posting I incorrectly posted my dosage in January 2016 as being 20mg/day. However the pills weren't 10mg but were the lowest commercial dosage of the brand Sprycel at 20mg each. So I was dosing at 40mg/day with a teaspoon of Quercetin for good measure.

 

Now I wish to dose at 100mg/day with as much or more Quercetin. This for an intial period of 2 weeks.

 

I've just ended a 2 week run of 10mg/day Epitalon, taken with 2mg/day of TB500 during the first week.

I will compare in its immediate perceived effects to a similar length run of 100mg of Dasatib with Quercetin.

 

Any ideas about my planned dosage will be appreciated. I could bump it up if some here think it worthwhile.

 

Cheers,

 

DareDevil

[DareDevil]

This doesn't modify my order in the group buy. However I jumped the gun and ordered a small first batch of 12 grams from TLR. It wasn't as expected in capsule form. It came in four small 3 gram packets of white Dasatinib powder and one large 120 gram packet of yellow Quercetin.

 

I will try some shortly, but am waiting to first end a bronchitis antibiotic treatment I am finishing to not sully my feedback.

 

Also, I was wondering what the bioavailability of oral Dasatinib might be since medical experimentation on mice has used injected forms of this drug and there is an online source for injectable Dasatinib. One could also try to dillute the powder in bacteriostatic water or injectable saline. Any ideas?

 

http://www.drugsdrop...mg-1665216.html

 

Of course, just like with its oral form, this would require experimental testing of dosage by researchers. I don't know if it might provide more benefits or reduce the cost of intake due to smaller doses required than oral ingestion? But it might be worth investigation, unless it could accentuate some of the unwanted side effects of Dasatinib. 

 

DareDevil

[Nate-2004]

Are we actually doing this group buy? Just wondering if it's going to happen or what the situation is. TLR isn't the source is it? I've not heard good things about that site, sketchy at best.

Edited by Nate-2004, 15 January 2017 - 10:45 PM.

[niner]

DareDevil, Dasatinib oral bioavailability is fine.  I wouldn't bother injecting it.  Researchers probably inject mice because it's easier than trying to get it down their throat.  They could put it in the mouse chow, but then they wouldn't know exactly how much the mice were getting.  It's possible that it tastes bad to mice as well.  Injections are just easier and more reliable for mouse experiments.

 

Edited by niner, 16 January 2017 - 06:45 AM.

[Logic]

Are we actually doing this group buy? Just wondering if it's going to happen or what the situation is. TLR isn't the source is it? I've not heard good things about that site, sketchy at best.

 

Group buys by their nature are done in ones spare time Nate.
I am currently still in Cape Town organising housing, swatting up on satellite internet for Mozambique and looking for ways to automate these buys more.
All on a 3G dongle with bad reception.

Ideally one would set up shopify to automate the whole process, leaving me free to do the research I enjoy, while getting all the components of my stack together affordably.
Sadly Shopify would require registering a business and registering for VAT here and cost a monthly fee of around $ 40.
Such a registered 'business' would also be a target for lawyers etc, and probably piss off Longecity management, so is not an option IMHO?

Getting names and address via PM and Email and copy pasting them into a spreadsheet and then working out each person's cost individually, with calculator, then sending it is very time consuming.
Also things can get very confusing when you have my type of 'crazy' and checking all my Emails etc again adds even more to the time reqd to organise this.
A properly set up spreadsheet that spits out the final cost when the amount and address is filled in is what has been side tracking my spare time recently.  I am not what one might call a Excel or Google Spreadsheets guru.  
Try integrating this into the desired spreadsheet:
https://www.paypal.c...-full#exhibit_A
And the Emails and PMs keep coming...

The Dasatinib is not from TLR.  That should be obvious due to the difference in price and the fact that the D will be tested by Mass Spectrography.

 

[Logic]

Dasatinib Group buy:

 

After going through all my Dasatinib Emails and PMs, I have copy-pasted my the Nic and amount columns from the spreadsheet below.
Please check that you are listed correctly and have all the required info from you before I send out the costings.
My new spreadsheet seems to be working well and will cut the time required to do so considerably.

 

REF.    Avatar                         Amount
R1C01 Ygdrasil                        10 g
R1C02 Vantika                       110 g
R1C03 Nate-2004                    10 g
R1C04 Fred_CALICO              10 g
R1C05 LookingForTime            5 g 
R1C06 Captain Obvious            5 g 
R1C07 rarefried                       10 g 
R1C08 Pampoenkop               10 g

R1C09 ClarkSims                    20 (40 if reqd)
R1C10 Searchingforanswers  10 g                               

R1C11 DareDevil                     50 g 
R1C12 niner                            10 (or more if reqd)

R1C13 Mikey                           10 g
R1C14 HomoLudens                 5 g  Address still reqd
R1C15 sthira                            10 g 
R1C16 Juliamoravcsik               5 g 
R1C17 Valijon                            2 g 
R1C18 Fafner55                       20 g                            
R1C19 eighthman                     10 g 

R1C21 tizak                                5 g 
R1C22 Katkay                           10 g
R1C23 Longevitarian                50 g             Address Required

R1C24 Authentic                         5 g 
R1C25 Robert Majka                 50 g
R1C26 jmorris                            20 g

R1C27 Ark                                   8 g
R1C28 Logic                              10 g

R1C29 Cosmicalstorm                 5 g

prophets                                       5 g

mkp6019                                      5 g             Address Required

Haste                                           5 g             Address Required

Rocket                                        10 g            Address Required  

   

Total                                         510 grams at the lower amounts

Edited by Logic, 16 January 2017 - 10:01 PM.