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[reason]

Nicotinamide adenine dinucleotide (NAD) is an important part of the mechanisms by which mitochondria produce chemical energy store molecules to power cellular processes. NAD levels fall with age, concurrent with growing mitochondrial dysfunction. There is some enthusiasm for approaches - such as supplementation with vitamin B3 derivatives - that might compensate for this issue and thereby improve mitochondrial function in later life.

Researchers here suggest that in fact the quality and quantity of evidence for NAD+ levels to decline with age doesn't rise to the level that the scientific community should by using as a basis to proceed towards the development of interventions. I think it most likely that more rigorous work will confirm the existing evidence. More pertinent objections to sizable investment in NAD upregulation are that (a) exercise increases NAD levels to a greater degree than any of the other approaches assessed to date, and (b) the results of clinical trials of NAD upregulation are decidedly mediocre.

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with age. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to increase NAD+ levels to promote vitality and protect against age-related diseases.

This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.

Link: https://doi.org/10.3390/nu14010101

View the full article at FightAging

[johnhemming]

I have been looking at the processes where Melatonin is generated in the Mitochondria  (one thing I do is to supplement with Melatonin to build up levels in the Mitochondria of cells throughout my body).   It appears that Melatonin is created from a substrate of Serotonin and Acetyl Co-A.  The Acetyl-CoA is created from Pyruvate.  This, however, can feed into the Krebs Cycle or be used to create Melatonin.  (it can probably be used for other things, but I don't know what they are)

 

The creation of Acetyl-CoA from Pyruvate requires NAD+.  Hence we have these questions

a) If Pyruvate is created at a rate greater than it can be processed into Acetyl-CoA then it hangs around in the Mitochondria doing damage.  The question here is what threshold of glycolysis is needed for this to happen and what would cause this is it a high level of serum glucosey

b) Once we have Acetyl-CoA it would either feed into the Krebs Cycle or be used as a substrate for AA-NAT to create Melatonin.   The question is what affects this.  I would think feeding into Krebs is the most likely outcome and only if there is a lot going into Krebs will we see spare Acetyl-CoA creating melatonin.

 

I am working on the assumption that the main benefit of Melatonin for most cells lies in protecting the Mitochondria and hence getting greater mitochondrial efficiency.

 

I also assume that Melatonin is consumed by the Mitochondria when acting as an anti-oxidant. I have done some experimentation on my gums for perio issues.  I find that Melatonin  (instant release pills held in the mouth hence having a high level in the mouth) massively calms down the inflammation, but if you don't take it for a day or two the inflammation gets worse.  I am making the assumption that this functions through protecting the mitochondria. Interestingly I managed last week to clear up an abscess with a combination of Melatonin and Malt Whisky.

 

Whichever way, you look at this, however, a shortage of NAD+ will result in a shortage of Acetyl Co-A.

 

 

 

 

Edited by johnhemming, 24 January 2022 - 07:10 PM.