NAM does not extend life span in mice
MikeDC
08 Mar 2018
The role in longevity and healthspan of nicotinamide (NAM), the physiological precursor of NAD+, is elusive. Here, we report that chronic NAM supplementation improves healthspan measures in mice without extending lifespan. Untargeted metabolite profiling of the liver and metabolic flux analysis of liver-derived cells revealed NAM-mediated improvement in glucose homeostasis in mice on a high-fat diet (HFD) that was associated with reduced hepatic steatosis and inflammation concomitant with increased glycogen deposition and flux through the pentose phosphate and glycolytic pathways. Targeted NAD metabolome analysis in liver revealed depressed expression of NAM salvage in NAM-treated mice, an effect counteracted by higher expression of de novo NAD biosynthetic enzymes. Although neither hepatic NAD+ nor NADP+ was boosted by NAM, acetylation of some SIRT1 targets was enhanced by NAM supplementation in a diet- and NAM dose-dependent manner. Collectively, our results show health improvement in NAM-supplemented HFD-fed mice in the absence of survival effects.
tunt01
08 Mar 2018
At first glance of the abstract, I thought what a worthless study. Then I see this was done by Rafael de Cabo's lab w/ Charles Brenner having some role.
Kind of interesting study. Maybe NAM is the answer for a HFD (Fig 1. 1G, etc.), not resveratrol. I'm sure MikeDC will think so.
Look at Figure 4A. Compensatory downregulation of NAMPT with NAM supplementation in controls (no HFD). Looks like there is no free lunch in NAD+ output. But then again, this is NAM not NR or NMN.
Any thoughts?
Edited by prophets, 08 March 2018 - 05:16 PM.
MikeDC
08 Mar 2018
At first glance of the abstract, I thought what a worthless study. Then I see this was done by Rafael de Cabo's lab w/ Charles Brenner having some role.
Kind of interesting study. Maybe NAM is the answer for a HFD (Fig 1. 1G, etc.), not resveratrol. I'm sure MikeDC will think so.
Look at Figure 4A. Compensatory downregulation of NAMPT with NAM supplementation in controls (no HFD). Looks like there is no free lunch in NAD+ output. But then again, this is NAM not NR or NMN.
Any thoughts?
Sinclair is also coauthor. Even though NAM was shown to have minor health effects against HFD, NR is much more effective. The down regulation of NAMPT is expected. You would expect much more down regulation of NAMPT from taking NAM than taking NR since NAM generated from NR and NAD+ consumption is spread out over a longer period while NAM supplementation is brute force. If you can maintain high NAD+ and down regulate NAMPT, then it is a good thing since NAMPT is pro inflammatory. The advantages of NR and NMN are they can increase NAD+ while down regulate NAMPT.
MikeDC
08 Mar 2018
Edited by MikeDC, 08 March 2018 - 05:33 PM.
