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Senolytics: A new research proposal targeting senescent fibroblasts with Piperlongumine

senolytics

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#1 Senescentis Salutem

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Posted 04 February 2017 - 06:10 AM


Senolytics represent a new class of senotherapeutics that target senescent cells. Currently 2 promising chemicals have been shown to effect selective senescent cell types namely Dasatinib (human fat cell progenitors) and quercetin (human endothelial cells and mouse BM-MSCs). Also the combination of dasatinib and quercetin appears to effect MEFs. [PMID: 25754370] While promising this leaves many other senescent cell types unaffected that need to be addressed. A compound known as piperlonguminine recently appears to preferentially effect fibroblast cells. [PMID: 27913811] but more research is needed. To that end I am planning on conducting a series of studies in vitro (cellular), in vivo (mice), and human to confirm both it's effectiveness and safety with the end goal of establishing it's effective safe dose in adults and bring a suitable therapy to market.

 

Your comments, criticisms, and feedback are duly welcomed.


Edited by Senescentis Salutem, 04 February 2017 - 06:18 AM.

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#2 eighthman

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Posted 08 February 2017 - 06:22 PM

https://www.scienced...31114132058.htm

 

I intuitively think that fast growing plants in particular may be useful in the search for safe and effective senolytics.  Any fast growing plant requires powerful mechanisms to maintain coherent growth so as to avoid ending up as a blob of tumors.  I recall that the Japanese demonstrated dramatic effects in vivo with lab rats and a cessation of induced tumor growth using simple seaweed extracts.  To regulate growth in one direction and inhibit it in another should require a senolytic action - or something very much like it.  I am interested in how the tagging or identification takes place so as to kill one cell while ignoring another.   

 

And my lawn is overrun with dandelions.....


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#3 sthira

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Posted 08 February 2017 - 07:46 PM

Eating dietary amounts of long pepper as an added spice may be tasty and beneficial. Long pepper then would be part of the dizzying array of other components found in vegetables and fruit. But to consume it as a be-dreamed of senolytic?

I posted this thread for discussions about piperlonguminine. Nothing else.


As is expressed elsewhere on this site, hoping to kill senescent cells by using big rude amounts of long pepper is still another unknown in a long ass list of other unknowns about what kills senescent cells safely, and what does not.

See, for example: http://www.longecity...mine-senolytic/

And more specifically, word up:

As I just posted elsewhere:
Folks, acting on this by swallowing large amounts of black pepper or Piper longum is madness ...
First, they haven't even shown that this stuff kills senescent cells in vivo, and we have no idea about a remotely rational dose for doing so. Second, we have no idea yet of the mechanism. Third, while the paper says that "the maximum tolerated dose in mice is very high," this is not remotely like safety data: it's based on the lack of acute toxic effects after 6 days' treatment.

And whether or not piperlongumine is safe or effective, swallowing mass amounts of pepper in hopes of getting an undefined minimum amoiunt of piperlongumine is not: piperine inhibits a range of xenobiotic-metabolizing enzymes, including the CYP450s and UDP-glucuronosyltransferase, potentially increasing the absorption of dietary carcinogens and other toxins (particularly in conjunction with the concomitant irritation of the intestinal wall). And while there are studies showing that piperine reduces the toxicity of endotoxin to cultured cells and tissue samples, it's entirely plausible that piperine-mediated increases in instestinal permeability could increase absorption of endotoxin, which increases systemic inflammation and has been implicated in atherosclerosis and a range of chronic diseases.

I repeat: they haven't even shown this stuff has senolytic effects in vivo yet, and are very far indeed from showing it's safe. Wait a while, OK? There's senolytic drugs and Oisín's non-integrating genetic senescent cell ablation system coming down the pipe, and they have animal data. There's nothing more embarrassing than dying prematurely from a foolish life extension experiment.


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#4 DareDevil

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Posted 26 February 2017 - 11:12 PM

Having tried Dasatinib with Quercetin and noting positive effects I am interested in more information about Piperlongumine. I have no idea how hard it would be to source it, i.e. for a Longecity Group Buy, and also wonder what risks its intake might carry. While it isn't exactly something likely to harm us in tiny doses if such substances exist already in dietary intake, it would be important to advance cautiously. From my experience killing senescent cells is something one notices when doing a brief protocol. It has a noticeable impact on one's physiological state and this reflects in how you feel and even to an extent in how you look. Small doses could possibly be experimented with cautiously. However, what constitutes a small enough dose is the question.

 

Cheers,

 

DareDevil

 


Edited by DareDevil, 26 February 2017 - 11:16 PM.

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#5 maxwatt

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Posted 27 February 2017 - 03:54 AM

Having tried Dasatinib with Quercetin and noting positive effects I am interested in more information about Piperlongumine. I have no idea how hard it would be to source it, i.e. for a Longecity Group Buy, and also wonder what risks its intake might carry. While it isn't exactly something likely to harm us in tiny doses if such substances exist already in dietary intake, it would be important to advance cautiously. From my experience killing senescent cells is something one notices when doing a brief protocol. It has a noticeable impact on one's physiological state and this reflects in how you feel and even to an extent in how you look. Small doses could possibly be experimented with cautiously. However, what constitutes a small enough dose is the question.

 

Cheers,

 

DareDevil

 

Well, that's one reason some of us keep pet mice.


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#6 DJSwarm

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Posted 19 January 2021 - 04:23 AM

Long pepper is a common spice. You can buy it to your heart's content from any good spice merchant, including various oils.

 

Looks like about $14 bucks for 200 grams of pods on amazon, though that seems a bit high. Note: it is hotter than Black Pepper.

 

Or get trikatu, a traditional Ayurvedic medicine - 1/3 long pepper, 1/3 black pepper, 1/3 ginger about $10 a pound

https://www.banyanbo...WxoC62kQAvD_BwE

 

 

 

 



#7 DJSwarm

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Posted 19 January 2021 - 04:26 AM

It is worth noting that pepper increases the bioavailability of many things. Be careful if you are taking other things:

https://www.ncbi.nlm...les/PMC3458266/

 







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