20 replies to this topic

[stefan_001]

The encouraging results led the researchers to test NR in a mouse model of Alzheimer's disease. Just like C. elegans, the mice saw a significant improvement of mitochondrial function and a reduction in the number of amyloid plaques. But most importantly, the scientists observed a striking normalization of the cognitive function in the mice. This has tremendous implications from a clinical perspective.

https://www.scienced...71206132526.htm

[Mind]

I enjoy your optimism, but must disagree a bit. Mouse studies very rarely translate into anything actionable for humans.

[Harkijn]

I agree with you, Mind,  but the optimism is not just Stefan's. The authors too are convinced of an important role for mitochondrial boosters. I found it worthwile to upload the full text here, but apparently I have no authorization to do so.

 

Edited by Harkijn, 07 December 2017 - 07:37 AM.

[stefan_001]

from the study:

"We also assessed the effect of NR on human Aβ-expressing neuroblastoma
cells and, consistent with the data from the C. elegans model,
we observed a remarkable reduction in intracellular Aβ deposits with
NR (Fig. 4l and Extended Data Fig. 6n), accompanied by increased
OXPHOS protein (Extended Data Fig. 5h) and MSR transcript levels
(Extended Data Fig. 6o)"

[Mind]

It is a good starting point. No doubt.

[Mike C]

Since when do mouse studies very rarely translate into anything actionable in humans. Thats news to me!

[Rocket]

Since when do mouse studies very rarely translate into anything actionable in humans. Thats news to me!

How about Dasatanib and Quercetin most recently. We know plenty about extending health and life in mice that doesn't translate into humans.

[stefan_001]

 

Since when do mouse studies very rarely translate into anything actionable in humans. Thats news to me!

How about Dasatanib and Quercetin most recently. We know plenty about extending health and life in mice that doesn't translate into humans.

 

 

I think the authors of this study tried to tackle this by spending part of their research on identification of a cross-species mitochondrial stress response signature. Its a study worth reading and it lines up with anecdotal evidence.

 

The dosing seems high:

mice were fed with pellets containing vehicle or NR (400 mg/kg/day)
for 10 weeks, starting at the age of 4 months. The pellets were prepared by mixing
powdered chow diet (2016S, Harlan Laboratories) with water or with NR dissolved
in water.

 

I am assuming this means body weight but it could be as part of diet. In any case quite high, in case they mean BW about 2g/day for 70kg person. However we have now seen a couple human data studies come out that show a diminishing return of higher dosing so it could well be you see the same results at lower doses.

 

Personally I will be giving cans of NR as Xmas presents to folks that I can see start declining. Its a small expense to keep people here a bit longer, there is so much anecdotal testomony in general about its positive effects that it is more than worth the try.
 

Edited by stefan_001, 08 December 2017 - 07:28 AM.

[sensei]

I enjoy your optimism, but must disagree a bit. Mouse studies very rarely translate into anything actionable for humans.

 

 

Then why all the hubbub surrounding Ichor's mouse trials of C60OO.

 

A bit hypocritical -- or cherry picking -- wouldn't you say?

[Harkijn]

Stefan said:

 

 

 

 

Personally I will be giving cans of NR as Xmas presents to folks that I can see start declining. Its a small expense to keep people here a bit longer, there is so much anecdotal testomony in general about its positive effects that it is more than worth the try.

 

 

 

Harkijn:

I agree wholeheartedly here. Finally a few pieces of this puzzle seem to come together. But let's keep in mind that mice don't normally suffer from Alzheimer's, so this 'animal model' is a very artificial one.
 

 

[stefan_001]

Sure its in mice but many here have followed mitochondrial health and so it should not really come as a surprise this study. Some past research making the link between NAD+ and ALZ:

https://www.frontier...2017.00377/full
https://www.scienced...891061817301230
https://www.scienced...043661817308368
https://www.ncbi.nlm.../?term=25884176
https://www.ncbi.nlm...pubmed/27130898
http://www.sciencedi...30439401730246X
http://www.sciencedi...197018617300955
https://www.ncbi.nlm...les/PMC5319230/

Edited by stefan_001, 08 December 2017 - 09:41 PM.

[bluemoon]

It is a good starting point. No doubt.

I've heard a 10% success rate from mice models but a lot of the failures are from cancer drugs where mice models have rarely been successful in that area. I assume researchers can also learn from mice model failures but not sure to what extent.

[Harkijn]

This article describes the complexity of using mice models in the study of ALZ:

http://www.alzforum....laque-free-mice

Edited by Harkijn, 09 December 2017 - 11:11 AM.

[Harkijn]

The EPLF website has a summary of Auwerx' research:

https://actu.epfl.ch...op-alzheimer-s/

[ceridwen]

I hate to burst your bubble but I'm on NMN and Im getting worse. Do you guys have any reason to believe that NR would work better and if so why?

[ceridwen]

I hate to burst your bubble but I'm on NMN and Im getting worse. Do you guys have any reason to believe that NR would work better and if so why?

[Harkijn]

I hate to burst your bubble but I'm on NMN and Im getting worse. Do you guys have any reason to believe that NR would work better and if so why?

Hi Ceridwen, this is not a personal experiences thread, so let's not derail things. Did you post somewhere else about your condition and fixing it with NMN?

[Michael]

Sure its in mice but many here have followed mitochondrial health and so it should not really come as a surprise this study. Some past research making the link between NAD+ and ALZ:

https://www.frontier...2017.00377/full
https://www.scienced...891061817301230
https://www.scienced...043661817308368
https://www.ncbi.nlm.../?term=25884176
https://www.ncbi.nlm...pubmed/27130898
http://www.sciencedi...30439401730246X
http://www.sciencedi...197018617300955
https://www.ncbi.nlm...les/PMC5319230/

 
Note, however, that these are all either studies in animal models, or reviews based on animal studies — or in the case of PMC5319230, a speculative story based on th role of the kynurenine pathway in AD and neuroinflammation, with only indirect touches on NAD+.

In this study, they report things that are the opposite of what you'd expect from the general story of the redox shift to low NAD:NADH in aging we've seen reported elsewhere: "Nicotinamide metabolites, including [total NAD⁺ + NADH] (a), NADH (b), and NAD⁺ (c) were decreased in LOAD [Late-Onset Alzheimer's Disease — ie "normal" AD driven by degenerative aging rather than severe familial mutations]samples compared to young and old controls, while the RRs (ratios NAD⁺/NADH) were not different between controls, but slightly increased in LOAD fibroblasts compared to all, young, and old control cells"
 

Edited by Michael, 11 December 2017 - 11:16 PM.

[ceridwen]

@Harkijin I don't think so
I think I have the family form any way having APP and PSEN2 mutations

[Harkijn]

@Harkijin I don't think so
I think I have the family form any way having APP and PSEN2 mutations

If this is about Huntingdon's disease, I think there is no way of telling if  either NMN or NR are effective at all.

You can give NR a try, of course, and since NR is cheaper than NMN it will be easier to take larger doses. This is very difficult for you. I hope you'll find improvement!

[stefan_001]

@Harkijin I don't think so
I think I have the family form any way having APP and PSEN2 mutations

If this is about Huntingdon's disease, I think there is no way of telling if either NMN or NR are effective at all.
You can give NR a try, of course, and since NR is cheaper than NMN it will be easier to take larger doses. This is very difficult for you. I hope you'll find improvement!

This is just in:

http://mobile.abc.ne...832?pfmredir=sm