459 replies to this topic

[corb]

 

What I find curious is that you have not seen improvement in wrinkles. Makes me wonder what is really happening perhaps it's all and only apoptotic pathway action on pre cancerous cells either benign or malicious.

 

Senescent cells aren't a big contributor to wrinkles.   The main contributors are photodamage and glycation.   Fafner's results suggest that pre-cancerous lesions (such as keratoses) are rich in senescent cells.  That makes a lot of sense.

 

 

I remember I linked a paper around the beginning of the thread that showed a link between cancerous formations and senescent cells.

Anyone interested in the topic can search it out. It's been an year maybe that research has progressed as well.
 

[stefan_001]

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2016-01-31, mid-afternoon No adverse symptoms. The thick patches of skin on my right arm that shrank about 70% in Experiment #8 are noticeably reduced further in the 5.5 hours since I started this morning, maybe by 30-40%. I did not see this effect with Experiment #9. I can’t be sure that this benefit is in fact senolytic or if it is just strongly apoptotic to precancerous cells. I don't notice any skin flaking. In any case, it is clearly beneficial to my skin.

5.5 hours seems too fast for that amount of shrinking of a skin lesion, particularly without flaking or peeling. Are you taking photographs?

5.5 hours is surprising fast. I was hesitant to post this result because it didn't seem credible, but that's what happened. It is possible that the patch of affected skin was particularly vulnerable to the apoptotic pathways put in play by these supplements. Last night, after 12 hours, those patches were further reduced in size and thickness to about 50% of their starting size. This morning (2015-02-01) they appear the same as last night.

It will be interesting to see if others get results from the same treatment.

Periodically I take pictures of my left hand to measure any benefit to wrinkles. It is quite difficult to get consistent lighting and comparable photos.

Honokiol has caused shrinking of some patches in my experience. When using it as topical some patches/flakes peel off and flatten . Interestingly some don't. I attributed that to apoptotic pathway.

What I find curious is that you have not seen improvement in wrinkles. Makes me wonder what is really happening perhaps it's all and only apoptotic pathway action on pre cancerous cells either benign or malicious.

I agree that my experiments 9 and 10 likely invoked apoptotic pathway action on precancerous cells and showed no clear indication of senolytic action. Experiment 8 which included dasatinib was different. The substantial amount of sun damaged skin that was shed as a result of that experiment must have resulted from apoptosis of senescent cells in addition to pre-cancerous cells. The skin on my chest, shoulders and back remains remarkably clear and smooth.

As for wrinkles, it has been 24 days since Experiment 8 (Jan 13) and I continue to see no effect on fine wrinkles. My expectation was that there would be remodeling of skin tissues as cells turned over, collagen gene expression hopefully restored and as fat layers returned to more youthful levels. But, I see no evidence of any of this.

That was my thinking as well. I have started to experiment with Fisetin (got some yesterday) as that would help with slowing glycation. I don't expect to see anything soon. But I am hoping that it would tilt the balance to my body being able to remove more glycation than new is created. But you may have a theory yourself perhaps :-) ?

[Fafner55]

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.

 

 

2016-01-31, mid-afternoon No adverse symptoms. The thick patches of skin on my right arm that shrank about 70% in Experiment #8 are noticeably reduced further in the 5.5 hours since I started this morning, maybe by 30-40%. I did not see this effect with Experiment #9. I can’t be sure that this benefit is in fact senolytic or if it is just strongly apoptotic to precancerous cells. I don't notice any skin flaking. In any case, it is clearly beneficial to my skin.

5.5 hours seems too fast for that amount of shrinking of a skin lesion, particularly without flaking or peeling. Are you taking photographs?

5.5 hours is surprising fast. I was hesitant to post this result because it didn't seem credible, but that's what happened. It is possible that the patch of affected skin was particularly vulnerable to the apoptotic pathways put in play by these supplements. Last night, after 12 hours, those patches were further reduced in size and thickness to about 50% of their starting size. This morning (2015-02-01) they appear the same as last night.
 

Honokiol has caused shrinking of some patches in my experience. When using it as topical some patches/flakes peel off and flatten . Interestingly some don't. I attributed that to apoptotic pathway.

 

 

 

Stefan_001, I can confirm your experience with honokiol shrinking some patches of skin.  I mixed honokiol with a few drops of grapeseed oil and applied it topically to the patches of (presumably) precancerous skin on my right arm.  It was well absorbed. The results were dramatic.  Within 6 or so hours the smaller of these patches nearly disappeared and the two larger ones dramatically reduced.

 

Add that to the arsenal.

[Bryan_S]

Nice article from MIT Technology Review delving into the business side of senolytics. Seems drugs have been devised to delay senescence as well as to eliminate those cells.

https://www.technolo.../set/id/600713/

 

I did some digging into Cancer biologist Jan van Deursen who was the one who claimed to see the connection. Here is a link to one of his papers from 2013.

http://www.isdbweb.o...ff116701067.pdf

 

There is a lot of other articles but his latest was published in Nature http://www.nature.co...l/nm.4000.html 

[stefan_001]

.
.

2016-01-31, mid-afternoon No adverse symptoms. The thick patches of skin on my right arm that shrank about 70% in Experiment #8 are noticeably reduced further in the 5.5 hours since I started this morning, maybe by 30-40%. I did not see this effect with Experiment #9. I can’t be sure that this benefit is in fact senolytic or if it is just strongly apoptotic to precancerous cells. I don't notice any skin flaking. In any case, it is clearly beneficial to my skin.

5.5 hours seems too fast for that amount of shrinking of a skin lesion, particularly without flaking or peeling. Are you taking photographs?

5.5 hours is surprising fast. I was hesitant to post this result because it didn't seem credible, but that's what happened. It is possible that the patch of affected skin was particularly vulnerable to the apoptotic pathways put in play by these supplements. Last night, after 12 hours, those patches were further reduced in size and thickness to about 50% of their starting size. This morning (2015-02-01) they appear the same as last night.

Honokiol has caused shrinking of some patches in my experience. When using it as topical some patches/flakes peel off and flatten . Interestingly some don't. I attributed that to apoptotic pathway.

Stefan_001, I can confirm your experience with honokiol shrinking some patches of skin. I mixed honokiol with a few drops of grapeseed oil and applied it topically to the patches of (presumably) precancerous skin on my right arm. It was well absorbed. The results were dramatic. Within 6 or so hours the smaller of these patches nearly disappeared and the two larger ones dramatically reduced.

Add that to the arsenal.

n=2 that's like the gold standard on the forum for efficacy. May I ask is there a reason you choose grapeseed oil from mixing and abortion perspective?

[Fafner55]

 

 

.
.

 

 

2016-01-31, mid-afternoon No adverse symptoms. The thick patches of skin on my right arm that shrank about 70% in Experiment #8 are noticeably reduced further in the 5.5 hours since I started this morning, maybe by 30-40%. I did not see this effect with Experiment #9. I can’t be sure that this benefit is in fact senolytic or if it is just strongly apoptotic to precancerous cells. I don't notice any skin flaking. In any case, it is clearly beneficial to my skin.

5.5 hours seems too fast for that amount of shrinking of a skin lesion, particularly without flaking or peeling. Are you taking photographs?

5.5 hours is surprising fast. I was hesitant to post this result because it didn't seem credible, but that's what happened. It is possible that the patch of affected skin was particularly vulnerable to the apoptotic pathways put in play by these supplements. Last night, after 12 hours, those patches were further reduced in size and thickness to about 50% of their starting size. This morning (2015-02-01) they appear the same as last night.

Honokiol has caused shrinking of some patches in my experience. When using it as topical some patches/flakes peel off and flatten . Interestingly some don't. I attributed that to apoptotic pathway.
 

Stefan_001, I can confirm your experience with honokiol shrinking some patches of skin. I mixed honokiol with a few drops of grapeseed oil and applied it topically to the patches of (presumably) precancerous skin on my right arm. It was well absorbed. The results were dramatic. Within 6 or so hours the smaller of these patches nearly disappeared and the two larger ones dramatically reduced.

Add that to the arsenal.

n=2 that's like the gold standard on the forum for efficacy. May I ask is there a reason you choose grapeseed oil from mixing and abortion perspective?

 

 

Grapeseed oil is primarily linoleic acid (70%).  Like olive oil (oleic acid), it has 18 carbons.  But unlike oleic acid, it has 2 cis bonds, shaping it into a sightly smaller molecule.  It also does not have as strong a fragrance as oleic or other similar fatty acids.  Together, these attributes make grapeseed oil a preferred ingredient for moisturizers in the cosmetic industry.  I know from experience that it is easily absorbed by the skin.

[Bryan_S]

On a whim I searched "NAD depletion Senescence Apoptosis Autophagy" After scanning some of the results I'm wondering for those of us on a NAD boosting regimen if we might be helping to hold on to some of our cellular baggage? As I scan these articles NAD depletion seems to be a necessary condition in this multi staged process of cells moving into senescence and later cell death. If this NAD stress is necessary to weed out these zombie cells maybe part of our future plan to eliminate senescence cells might be a washout period where we stop any NAD boosting some days before taking our senolytic drugs.

 

This is speculation but I wouldn't want to rescue the same cells I was wanting to eliminate. Any opinions?

Edited by Bryan_S, 09 February 2016 - 12:35 AM.

[Fafner55]

On a whim I searched "NAD depletion Senescence Apoptosis Autophagy" After scanning some of the results I'm wondering for those of us on a NAD boosting regimen if we might be helping to hold on to some of our cellular baggage? As I scan these articles NAD depletion seems to be a necessary condition in this multi staged process of cells moving into senescence and later cell death. If this NAD stress is necessary to weed out these zombie cells maybe part of our future plan to eliminate senescence cells might be a washout period where we stop any NAD boosting some days before taking our senolytic drugs.

 

This is speculation but I wouldn't want to rescue the same cells I was wanting to eliminate. Any opinions?

 

I wondered about the same thing.

 

It isn't certain, but research suggests that nicotinamide riboside could inhibit the caspase cascade and suppress apoptosis.

1. “Mitigation of gamma-radiation induced abasic sites in genomic DNA by dietary nicotinamide supplementation: metabolic up-regulation of NAD(+) biosynthesis.” (2013) http://www.ncbi.nlm.nih.gov/pubmed/23891603

2. “NAD+ acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration“ (2013) http://www.ncbi.nlm.nih.gov/pubmed/23975935

 

I took NR not the day of but the day before my experiment #8.

[Bryan_S]

 

On a whim I searched "NAD depletion Senescence Apoptosis Autophagy" After scanning some of the results I'm wondering for those of us on a NAD boosting regimen if we might be helping to hold on to some of our cellular baggage? As I scan these articles NAD depletion seems to be a necessary condition in this multi staged process of cells moving into senescence and later cell death. If this NAD stress is necessary to weed out these zombie cells maybe part of our future plan to eliminate senescence cells might be a washout period where we stop any NAD boosting some days before taking our senolytic drugs.

 

This is speculation but I wouldn't want to rescue the same cells I was wanting to eliminate. Any opinions?

 

I wondered about the same thing.

 

It isn't certain, but research suggests that nicotinamide riboside could inhibit the caspase cascade and suppress apoptosis.

1. “Mitigation of gamma-radiation induced abasic sites in genomic DNA by dietary nicotinamide supplementation: metabolic up-regulation of NAD(+) biosynthesis.” (2013) http://www.ncbi.nlm.nih.gov/pubmed/23891603

2. “NAD+ acts on mitochondrial SirT3 to prevent axonal caspase activation and axonal degeneration“ (2013) http://www.ncbi.nlm.nih.gov/pubmed/23975935

 

I took NR not the day of but the day before my experiment #8.

 

 

I think you're right. I think as these drugs become more targeted to specific tail tell senescence markers this may become a non issue. But with all the data I've accumulated on NR specifically and NAD boosting in general I think we might be defeating the effort if we keep NAD levels high during senolytic treatments. We will see if a consensus develops as more people weigh in.

Edited by Bryan_S, 09 February 2016 - 01:32 AM.

[niner]

Guys, I think you may have hit on something important.  A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic.  It would probably be a good idea to have an NR washout period prior to senolytic treatment.  You could probably add c60oo to the washout list, too. 

[Bryan_S]

By the way Josh Mitteldorf put together a nice overview of many of the details we've accumulated on this thread. He posted it yesterday. 

 

http://joshmitteldor...og.com/2016/02/

[Logic]

A nice easy and informative read on senescent cells:

Four faces of cellular senescence

http://jcb.rupress.o.../192/4/547.full

 

You may be interested in the progerin thread.  More ....nib goodness:

http://www.longecity...licin/?p=761553

[Antonio2014]

Strange, but now the link works for me. Thanks! I will read it carefully.

[sthira]

Guys, I think you may have hit on something important. A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic. It would probably be a good idea to have an NR washout period prior to senolytic treatment. You could probably add c60oo to the washout list, too.

Would it also be a good idea to have a food and all supplement washout period for three to five days? Are there benefits here of water-only fasting?

[Bryan_S]

Guys, I think you may have hit on something important.  A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic.  It would probably be a good idea to have an NR washout period prior to senolytic treatment.  You could probably add c60oo to the washout list, too. 

 

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

 

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

 

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

[Logic]

Following this reasoning makes wonder if mebendazole could be another option for get rid off senescent cells.

The combination with c60 and PQQ apparently worked very well for the dog:
 
Does anyone else know if Mebendazole share some other mechanism of action with Dasatinib? or if this conjeture has some more support?

Thx for reminding me about mebendazole Bierak.
 
Here is a quote of my post in the 'Dog with bowel cancer' thread: (it lived well for another 1.5 years and died at age 14, after being given 2 weeks to live)
 
I agree that mebendazole works on worms by destabilising microtubules, but there is evidence that it has a similar effect on cancer cells and is effective despite your doubts about bioavailability:
 

The Anthelmintic Drug Mebendazole Induces Mitotic Arrest and Apoptosis by Depolymerizing Tubulin in Non-Small Cell Lung Cancer Cells:
http://www.ncbi.nlm....ng Cancer Cells

Mebendazole Elicits a Potent Antitumor Effect on Human Cancer Cell Lines Both in Vitro and in Vivo:
http://www.ncbi.nlm....tro and in Vivo

Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells:
http://www.ncbi.nlm.... Melanoma Cells

Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice:
http://www.ncbi.nlm....ed in nude mice

Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme:
http://www.ncbi.nlm....toma multiforme

...As well as destabilising microtubules Mebendazole has also been shown to boost OXPHOS expression while suppressing ROS levels, as has deoxysappanone B, found in Green Tea and most other microtubule destabilizers...

http://www.longecity...ndpost&p=593124

 
So Mebendazole is worth a look as a cheap and easily available (here) alternative or adjunct to Dasatinib.  (Its not available in the USA and UK anymore.  Probably because of the above effects.)

The question is:  
How strong is it? ie: What dose is required to be the equivalent of 300 mg of D?

 

The full text of:

 

Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells

http://mcr.aacrjourn...t/6/8/1308.long

 

...Figure 2A shows that 24 h after cells were treated with 1 μmol/L mebendazole, 25% of M-14 cells and 31% of SK-Mel-19 were positive for Annexin V staining, indicating that these cells were undergoing apoptosis...

 

...We identified Bcl-2 as a critical mediator of the differential cellular response to mebendazole treatment in melanocytes versus melanoma cells. After mebendazole treatment, Bcl-2 is rapidly phosphorylated in melanoma cells but not in melanocytes. In the literature, the functional significance of Bcl-2 phosphorylation remains controversial. Some reports suggest that Bcl-2 phosphorylation renders the protein inactive and cells more sensitive to induction of apoptosis (15), whereas other studies suggest that the antiapoptotic function of Bcl-2 is enhanced by phosphorylation (40). The differing consequences of Bcl-2 phosphorylation may be attributed to the agent used to induce phosphorylation in these studies. When antimitotic agents are used to induce Bcl-2 phosphorylation, this typically results in Bcl-2 inactivation. Consistent with this notion, our data suggest that tubulin-disrupting mebendazole causes Bcl-2 phosphorylation, which prevents its interaction with proapoptotic Bax, thereby promoting selective apoptosis in melanoma cells. Furthermore, we show that reduction of Bcl-2 protein levels through RNA interference sensitized initially mebendazole-resistant melan-a melanocytes to the growth-inhibitory properties of mebendazole. This result further supports the importance of Bcl-2 in the differential cellular responses between melanoma cells and melanocytes to mebendazole-mediated growth inhibition. In contrast, Sasaki et al. (7) reported that Bcl-2 phosphorylation was not a necessary event for mebendazole-induced apoptosis in non–small cell lung carcinoma cells based on the observation that Bcl-2 phosphorylation occurred in response to mebendazole treatment in H460 cells but not in A549 cells. However, it should be noted that A549 cells seem to express little or no Bcl-2 protein, whereas both the melan-a and M-14 cells used in our study express comparable levels of Bcl-2 protein, readily detectable by Western blotting (Fig. 4). In addition, Bcl-2 phosphorylation was observed in other melanoma cell lines (Yusac-2 and SK-Mel-19) treated with mebendazole (data not shown). These differences might explain the discrepancies between our work and the results reported by Sasaki et al...

 

 

So it looks like a god adjunct to get rid certain cancerous cells, but not as a replacement for D?

Note that all these compounds seem to be specific to certain cell types, so a cocktail of D, Q, M and Navitoclax probably has additive and possibly synergistic effects?

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

 

Also is 1 μmol/L achievable?

 

Cimetidine increases serum mebendazole concentrations. Implications for treatment of hepatic hydatid cysts.

http://www.ncbi.nlm....les/PMC1386263/

Edited by Logic, 11 February 2016 - 09:57 PM.

[BieraK]

The common dosage for cancer is 100 mg twice a day.

Both, dasatinib and mebendazole shares some mechanisms:

The main targets of dasatinib are BCR/Abl (the "Philadelphia chromosome"), Src, c-Kit, ephrin receptors, and several other tyrosine kinases.

https://en.wikipedia.../wiki/Dasatinib

 Furthermore, MBZ, but not ABZ, was found to significantly interact with several protein kinases including BCR–ABL and BRAF

 In CMAP, the MBZ-induced gene expression profile correlated strongly with nocodazole a well-known tubulin inhibitor with chemical structure similarity to MBZ. Also nocodazole has recently been shown to inhibit several protein kinases including Bcr–Abl (Park et al. 2012). These results thus suggest additional potential targets of importance for MBZ efficacy.

http://www.ncbi.nlm....les/PMC3825534/
Nocodazole is a High-Affinity Ligand for the Cancer-Related Kinases ABL, c-KIT, BRAF, and MEK
http://dx.doi.org/10.../cmdc.201100410

[stefan_001]

 

Guys, I think you may have hit on something important.  A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic.  It would probably be a good idea to have an NR washout period prior to senolytic treatment.  You could probably add c60oo to the washout list, too. 

 

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

 

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

 

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

 

 

Somehow this reasoning leads to weird conclusions.... This discussion earlier highlights that senescent cells have much in common with cancer cells except that they dont divide. Hence cancer medication might be options to remove them. So if above hunch would be correct than likely NAD+ boosting helps cancer survive during treatment also...

Edited by stefan_001, 12 February 2016 - 10:40 AM.

[corb]

 

 

Guys, I think you may have hit on something important.  A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic.  It would probably be a good idea to have an NR washout period prior to senolytic treatment.  You could probably add c60oo to the washout list, too. 

 

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

 

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

 

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

 

 

Somehow this reasoning leads to weird conclusions.... This discussion earlier highlights that senescent cells have much in common with cancer cells except that they dont divide. Hence cancer medication might be options to remove them. So if above hunch would be correct than likely NAD+ boosting helps cancer survive during treatment also...

 

 

But it does!

Why wouldn't it!

NAD inhibitors are an emerging cancer therapy.

[stefan_001]

Guys, I think you may have hit on something important. A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic. It would probably be a good idea to have an NR washout period prior to senolytic treatment. You could probably add c60oo to the washout list, too.

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

Somehow this reasoning leads to weird conclusions.... This discussion earlier highlights that senescent cells have much in common with cancer cells except that they dont divide. Hence cancer medication might be options to remove them. So if above hunch would be correct than likely NAD+ boosting helps cancer survive during treatment also...

But it does!
Why wouldn't it!
NAD inhibitors are an emerging cancer therapy.

True I recall reading somewhere that at least for some cancers NAD level are abnormally low and lowering them further would push them over the edge. So if that were the case also for senescent cells than apart from stopping supplementation one should also take NAMPT inhibitors together with synoletics

Edited by stefan_001, 12 February 2016 - 08:51 PM.

[Bryan_S]

But it does!

Why wouldn't it!

NAD inhibitors are an emerging cancer therapy.

 

 

This is correct some cancer therapies target NAD metabolism to kill cancer. In this instance logic would dictate NR would be contraindicated as it would defeat that type of treatment. Different cancers need different strategies so the Oncologist in charge of the chemotherapy would need to know what what the subject was taking before hand.

[Logic]

 

 

 

 

Guys, I think you may have hit on something important. A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic. It would probably be a good idea to have an NR washout period prior to senolytic treatment. You could probably add c60oo to the washout list, too.

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

Somehow this reasoning leads to weird conclusions.... This discussion earlier highlights that senescent cells have much in common with cancer cells except that they dont divide. Hence cancer medication might be options to remove them. So if above hunch would be correct than likely NAD+ boosting helps cancer survive during treatment also...

But it does!
Why wouldn't it!
NAD inhibitors are an emerging cancer therapy.

True I recall reading somewhere that at least for some cancers NAD level are abnormally low and lowering them further would push them over the edge. So if that were the case also for senescent cells than apart from stopping supplementation one should also take NAMPT inhibitors together with synoletics

 

 

"NAMPT inhibitors"...?  
NAMPT is what recycles NAM to NAD+ IIRC right?
Do you know of any?

Better yet; do you know of any NAMPT activators?

[stefan_001]

 

 

 

 

 

Guys, I think you may have hit on something important. A high NAD+ level is a mark of a healthy cell, and healthy cells shouldn't be going apoptotic. It would probably be a good idea to have an NR washout period prior to senolytic treatment. You could probably add c60oo to the washout list, too.

Someone who I believe was browsing this board posted a similar question on the Nicotinamide Riboside board.

What are the effects of Nicotinamide Riboside on autophagy? We didn't go that far as to answer that question in this forum.

I took a stab at it and it involved a night of reading and I think I hit all the appropriate facets. Those who are more knowledgeable are welcome to contribute and it has some bearing on what we discussed.

Somehow this reasoning leads to weird conclusions.... This discussion earlier highlights that senescent cells have much in common with cancer cells except that they dont divide. Hence cancer medication might be options to remove them. So if above hunch would be correct than likely NAD+ boosting helps cancer survive during treatment also...

But it does!
Why wouldn't it!
NAD inhibitors are an emerging cancer therapy.

True I recall reading somewhere that at least for some cancers NAD level are abnormally low and lowering them further would push them over the edge. So if that were the case also for senescent cells than apart from stopping supplementation one should also take NAMPT inhibitors together with synoletics

 

 

"NAMPT inhibitors"...?  
NAMPT is what recycles NAM to NAD+ IIRC right?
Do you know of any?

Better yet; do you know of any NAMPT activators?

 

 

 

 

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer.

http://www.ncbi.nlm....pubmed/25709099

 

Discovery of Novel Inhibitors and Fluorescent Probe Targeting NAMPT

http://www.ncbi.nlm....les/PMC4521150/

 

 

Edited by stefan_001, 14 February 2016 - 12:59 PM.

[Logic]

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer.
http://www.ncbi.nlm....pubmed/25709099
 
Discovery of Novel Inhibitors and Fluorescent Probe Targeting NAMPT
http://www.ncbi.nlm....les/PMC4521150/

Damn!: No NAMPT upregulators...

[stefan_001]

 

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer.
http://www.ncbi.nlm....pubmed/25709099
 
Discovery of Novel Inhibitors and Fluorescent Probe Targeting NAMPT
http://www.ncbi.nlm....les/PMC4521150/

Damn!: No NAMPT upregulators...

 

 

try taking a very deep breath :-) and relax

http://www.ncbi.nlm....pubmed/24821571
 

[Logic]

 

 

Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer.
http://www.ncbi.nlm....pubmed/25709099
 
Discovery of Novel Inhibitors and Fluorescent Probe Targeting NAMPT
http://www.ncbi.nlm....les/PMC4521150/

Damn!: No NAMPT upregulators...

 

 

try taking a very deep breath :-) and relax

http://www.ncbi.nlm....pubmed/24821571
 

 

 

Chill-Chill!  

I haven't read the studies yet due to their titles, but they will probably contain some leads.

Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1

http://www.pnas.org/...9/39/15888.full

Probably more-so, and ties in with my new pet theory, but also unread as yet.

Now; WTF are we doing in the Senolytics thread!?

Soz guys.  

[stefan_001]

Ok I started my own mini experiment but only with Pterostibene (500mg) and Magnolia Extract (480mg) + couple caps Ginkho for circulation. Both of them have strong anti cancer impact so here's hoping Senecent cells are fit into some of the character is those are effective on. I am maintaining however the NR at 2 x 250mg a day. Will do this a week then have a week break and do the same without NR.

[corb]

 

Cellular senescence is a state of permanent growth arrest and is thought to play a pivotal role in tumor suppression. Cellular senescence may play an important role in tumor suppression, wound healing, and protection against tissue fibrosis in physiological conditions in vivo. However, accumulating evidence that senescent cells may have harmful effects in vivo and may contribute to tissue remodeling, organismal aging, and many age-related diseases also exists. Cellular senescence can be induced by various intrinsic and extrinsic factors. Both p53/p21 and p16/RB pathways are important for irreversible growth arrest in senescent cells. Senescent cells secret numerous biologically active factors. This specific secretion phenotype by senescent cells may largely contribute to physiological and pathological consequences in organisms. Here I review the molecular basis of cell cycle arrest and the specific secretion phenotype in cellular senescence. I also summarize the current knowledge of the role of cellular senescence in vivo in physiological and pathological settings.

 

http://www.pathobiol...icle/view/27743

 

Reading through this article I find that all the beneficial effects of cellular senescence listed can be surmised with activating the immune system to clean up the junk and promoting wound healing, again through the immune system, it's a "mediator" (more like an instigator) role rather than anything else.

It seems the only reason for senescent cells to exist is to drive the immune system into a frenzy. I don't see how any of these benefits can be achieved in an old individual.
All of the beneficial effects were studied in induced disease models in young animals. So take it with an extra grain of salt.

 

 

[stefan_001]

Ok I started my own mini experiment but only with Pterostibene (500mg) and Magnolia Extract (480mg) + couple caps Ginkho for circulation. Both of them have strong anti cancer impact so here's hoping senecent cells fit into some of the characteristics those are effective on. I am maintaining however the NR at 2 x 250mg a day. Will do this a week then have a week break and do the same without NR.

So I did this for a week and went back to normal supplementation after that. I look fine, perhaps slightly better skin tone but the wrinkles have not changed too much, at best slightly less deep. While it might have done nothing at all I am also wondering whether the expectation of fast results is completely unrealistic. I could imagine that they are hard to kill and only few die per round - removal to take years?

Edited by stefan_001, 27 February 2016 - 07:44 PM.

[stefan_001]

Not sure was this already posted:
http://www.nature.co...ature16932.html

Or this:
More speculatively, given that the SASP has been implicated in numerous other age-related disorders, it will be worth testing the effects of MLL1 inhibition in other aging and inflammatory disease models."
http://www.science20...d_cancer-164909

Edited by stefan_001, 27 February 2016 - 09:37 PM.