36 replies to this topic

[MikeDC]

That is 100% incorrect.

This study proved conclusively that NRK1 is NOT required.

Now, you can say that NRK1 is still important - which is what Dr Sinclair says in the study.

But it does prove the existence of a transporter that does not require NRK1, and can not transport NR.

It is specific for NMN, and does not involve NR or NRk1 at all.

This study didn’t show any data that NRK1 is not required. It just said that since NAD+ in cells are increased quickly, NMN must be getting into cells intact. The logic is wrong.

[able]

This study didn’t show any data that NRK1 is not required. It just said that since NAD+ in cells are increased quickly, NMN must be getting into cells intact. The logic is wrong.

 

 

Seriously?  You are arguing with the central finding of the study?   You know more than Dr Imai and Sinclair?  Wow, stunning.

[MikeDC]

Seriously? You are arguing with the central finding of the study? You know more than Dr Imai and Sinclair? Wow, stunning.

That is not the central conclusion of the study. They found a transporter for NMN. This does’t invalidate previous findings. It is consistent with previous studies. NMN transport is neglible compared to NR transport. That is why NRK1 is required for NMN to increase NAD+.

[able]

That is not the central conclusion of the study. They found a transporter for NMN. This does’t invalidate previous findings. It is consistent with previous studies. NMN transport is neglible compared to NR transport. That is why NRK1 is required for NMN to increase NAD+.

 

 

They found a transporter that is specific for NMN.

It does NOT require nrk1 or NR to convert to NAD+. At all.  Please stop saying this.

 

Of course it doesn't mean nrk1 is not needed to keep NAD+ levels up.   

 

It just means there IS an alternative pathway that NMN can take.

 

It might be important, as it bypasses the liver.  It creates NAD+ directly and very quickly  from the small intestine.  

 

This alternative pathway doesn't go thru NR. 

 

It is an additional pathway that NR CANNOT USE.

 

It might be a tiny fraction and not significant, or it might increase and be significant in older animals.  

 

You have absolutely no idea how much it is used. 

Edited by able, 20 February 2019 - 06:17 PM.

[MikeDC]

They found a transporter that is specific for NMN.
It does NOT require nrk1 or NR to convert to NAD+. At all. Please stop saying this.

Of course it doesn't mean nrk1 is not needed to keep NAD+ levels up.

It just means there IS an alternative pathway that NMN can take.

It might be important, as it bypasses the liver. It creates NAD+ directly and very quickly from the small intestine.

This alternative pathway doesn't go thru NR.

It is an additional pathway that NR CANNOT USE.

It might be a tiny fraction and not significant, or it might increase and be significant in older animals.

You have absolutely no idea how much it is used.

I agree they found a pathway that doesn’t require NRK1. My point is the pathway is extremely small like a needle compared to NR pathway that is like a big pipe. The NMN pathway in cells other than intestine can’t be detected. The small amount of NMN that gets into the blood from intestine is also very small and no larger than NR as shown by Ling Liu‘s data. Rather call it NMN transporter, you can call it NMN leaker. You can’t call something a transporter when it is practically zero.

[able]

I agree they found a pathway that doesn’t require NRK1. My point is the pathway is extremely small like a needle compared to NR pathway that is like a big pipe. The NMN pathway in cells other than intestine can’t be detected. The small amount of NMN that gets into the blood from intestine is also very small and no larger than NR as shown by Ling Liu‘s data. Rather call it NMN transporter, you can call it NMN leaker. You can’t call something a transporter when it is practically zero.

 

 

Ok, we're making progress.

 

I agree it is likely a small quantity.  It might be insignificant.  It might be an "NMN leaker".  

 

But there is no evidence yet how much it is utilized, or how much it is capable of transporting.

 

The research clearly shows it gets upregulated in older, sicker animals.  

 

You don't know how much it gets utilized.  They didn't measure that. Just that the genes and protein are more prevalent in low NAD+ conditions.  You don't know the capability.

 

As I said several times, and you don't refute - The Liu study used young, healthy animals, so wouldn't expect to see any utilization of Slc12a8 in those.

[MikeDC]

Ok, we're making progress.

I agree it is likely a small quantity. It might be insignificant. It might be an "NMN leaker".

But there is no evidence yet how much it is utilized, or how much it is capable of transporting.

The research clearly shows it gets upregulated in older, sicker animals.

You don't know how much it gets utilized. They didn't measure that. Just that the genes and protein are more prevalent in low NAD+ conditions. You don't know the capability.

As I said several times, and you don't refute - The Liu study used young, healthy animals, so wouldn't expect to see any utilization of Slc12a8 in those.

By inhibiting NAMPT, Slc12a8 is over expressed by 20%. 20% over nothing is still nothing. Previous studies showed that when NRK1 is KO, NMN doesn’t increase NAD+ inside cells. The authors should have repeated the same experiment.