Why does NAD+ decrease as we age?

NAD+ levels decrease during aging through two main mechanisms. The first one is reduced biosynthesis—the older we get, the less NAD+ is produced by the body, possibly due to oxidative stress and chronic inflammation.^[1] The second mechanism is thought to be increased NAD+ consumption. Increased activity of NAD+-dependent enzymes, coupled with a decreased total pool of available NAD+, creates a situation where there’s not enough NAD+ to support maximal function of the dependent enzymes. For example, DNA damage tends to increase during aging, causing PARP enzymes to consume more NAD+, leaving less of this cofactor available to support the function of other enzymes, such as the sirtuins.