Peter Attia· MD
nad levels decline in aging you lose so joint activity declines which is not good right because you now lose the ability to control easy to control gene expression
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nad levels decline in aging you lose so joint activity declines which is not good right because you now lose the ability to control easy to control gene expression
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either honestly you boost the nad as it's declining and uh you get a little bit increase in search of an activity right right
as the race as we age it has been postulated and maybe even observe that oh I don't know if it's been truly observed inside the mitochondria maybe it has that the ratio of nad to NADH goes down and if that's happening then you have presumably less nad with nad being an important substrate for sirtuins which do many things but primarily repair DNA damage
the prediction would be that you would have declining sirtuin activity due to that metabolic shift and i will also note because i think this is important that in mitochondrial disease you see the same shift it's just much much more pronounced you see a shift towards nadh and less nad and that's exactly what you see when mitochondria are less functional because the cells will switch over to glycolysis and fermentation right fermentation to lactate and the whole reason why we ferment to lactate is to restore nad levels right fermentation to lactate takes nadh and turns it back into nad so it this probably reflects an underlying metabolic defect which could be mitochondrial in origin that leads to this shift towards towards the reduced form of nad with age so so those two observations less nad right bad sirtuin's good the prediction is that that if we could boost nad that would be good because that would then restore sirtuin activity and have effects on aging
sirtuins are nad dependent enzymes right so they need nad to do their action and we've already talked about in general the model is that turning up sirtuins is is is a good thing right that you're going to get if you're going to get benefits in the context of aging
So if the NAD levels change as we know they do during aging, it will lead to a change in the activity of the of the suins.
So if the NAD levels change as we know they do during aging, it will lead to a change in the activity of the of the suins.
One thing that your your listeners should know about um uh about NAD levels and why the decrease in NAD levels are relevant to aging is with respect to the certuins because sertuins have a relatively narrow range of KD for NAD.
One of the consequences is that enzymes like sirtuins which rely on NAD to exert all of their beneficial activities actually function less well. That’s what happens during aging. But, also many other enzymes that are involved in our metabolism are relying on NAD, and so they function less well, so your intermediary metabolism functions less well.
And there’s growing evidence that its level decrease during aging.
But the NAD in your mitochondria inside your cells, you know, is pretty good in your teens, 20s, and 30s, but then in your 40s into your 50s, it falls off rapidly.
So just when you need more active sirtuins as the DNA damage is increasing, the fuel supply for the sirtuins starts plummeting, and then all of a sudden, you're not able to, you know, control your epigenome, and we get aging, we get aging significantly.