We know that NAD+ levels in our body naturally decline as we age. By age 40, levels of NAD+ have declined by 50% and this increases to 80% by age 60. NAD+ is intrinsically linked to the ageing process and our cellular health. But why do our NAD+ levels decline like this as we age?
NAD+ declines with age because it is destroyedResearch has shown that over time, NAD+ is actively destroyed by the enzyme CD38. CD38 is a membrane-bound NADase that hydrolyzes NAD+ to nicotinamide and (cyclic-)ADP-ribose. It’s associated with immune responses and energy metabolism, but it’s also a NADase whose levels rise with ageing, with a corresponding increase in NADase activity and a decrease of NAD+. Put plainly, CD38 requires NAD+ to function and while active, it binds and consumes specific parts of the molecule.
The mechanisms of ageing also contribute to NAD+ declineAdditionally, the common mechanisms of ageing, including oxidative stress, decline in mitochondria production and gene expression, DNA function, and healthy inflammation responses, all lead to NAD+ decline.
Salvage pathway vs. de novo pathwayTo produce NAD+, two main pathways are involved. The first is called the de novo pathway, which uses the essential amino acid L-tryptophan. De novo pathways require precursors that can only be obtained from the diet. The second is called the salvage pathway, which uses the molecules NA, NAM, NMN and NR. The main source of NAD+ production is this salvage pathway but unfortunately, this pathway appears to be disrupted with age, possibly due to a reduction in NAMPT, an enzyme that inhibits the salvage pathway.
Consequences of low NAD+Because NAD+ is so intrinsic to a variety of vital internal functions on a cellular level. The consequences of low NAD+ levels can be quite far reaching and can include:
- Premature ageing
- Skin damage
- Immune system issues
- Increased stress and anxiety
- Excess fatigue
- Weight gain
- Brain fog and lack of mental clarity
- Low concentration levels