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NAD (Nicotinamide adenine dinucleotide) and aging - does differential expression of KYNU and KMO genes reduce NAD levels.

Nicotinamide adenine dinucleotide (NAD) is a chemical found in cells which is at the centre of many metabolic processes. It has been noted by many people that NAD levels go down as people get older. I won't go into any of the details of the impact of this as it can be read in many other places. This is just one of many articles about this. I am not citing it particularly, but it is one I found in a few second searching on the net.

Recently Michael Lustgarten produced a video:

I have linked to the video to a point at which the alternative route of producing NAD from Tryptophan is highlighted

Most of the discussions about NAD relate to how it is produced from different versions of vitamin B3 which includes NMN and NR. Indeed there have been many debates about what is the best way to increase NAD+.

The video got me thinking. The video highlights how there is an increase in the metabolite (3-hydroxy-l-kynurenine) produced by Kynurenine 3-monooxygenase (which is produced by the KMO gene) with age, but a reduction in the metabolite (Anthranilic acid) produced by Kynureninase (which is produced by the KYNU gene) with age. The consequence of this is a reduction in the production of NAD+ by this pathway.

Michael suggests that additional Vitamin B6 would cause an increase in the activity of Kynurenine 3-monooxygenase and he is experimenting to see what happens. However, his video made me wonder if we would expect a varation in the expression of KYNU which was separate to one of KMO. So I looked at the genes:

KMO linked on is Chromosome 1: 241,532,134-241,595,642 63.5 kilo base pairs
KYNU linked on is Chromosome 2: 142,877,657-143,055,833 178 kilo base pairs

So KYNU is clearly longer than KMO and we would expect a relative reduction in transcription of KYNU compared to KMO. The only research data I have found in fact finds an increase in mRNA for KYNU with age and a reduction in KMO. Whether that means that without the aging process the situation would be more extreme or not I don't know. It remains, however, that this particular pathway can affect NAD levels.


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