Why do NAD⁺ levels decline as we age?Updated 3 months ago

There are three explanations for this:

1. Increased breakdown by enzymes: 
   The activity of NAD⁺-consuming enzymes, particularly CD38 (which destroys NAD⁺) and PARPs (which consume NAD⁺ for DNA repair), increases with age.
2. Reduced recycling capacity:
   The efficiency of the salvage pathway—the main route for NAD⁺ regeneration and recycling—declines as the activity of the crucial enzyme NAMPT decreases with age.
3. Stimulation by inflammation:
   Chronic, low-grade inflammation (inflammaging) stimulates the overexpression and activity of NAD⁺-degrading enzymes such as CD38, further accelerating its breakdown.