What is NAD+ and why does it decline as you age?

NAD+ is a coenzyme that is active in virtually every cell of your body. Its first role is to convert nutrients into usable energy. It also acts as a helper molecule for a range of proteins that repair DNA damage, regulate gene activity, clear out aged cells and direct the immune system. Without sufficient NAD+, all of those processes falter at the same time.

NAD+ levels decline steadily as you get older. This has been measured in tissues from both mice and humans, and the pattern is consistent. One important cause lies in a chain reaction of low-grade inflammation. Senescent cells accumulate in fat tissue and the liver and secrete inflammatory substances. Those substances attract a particular type of immune cell (a pro-inflammatory macrophage), and that type contains high levels of an enzyme that actively breaks down NAD+. The result: the more of those cells are present in your tissue, the faster NAD+ is used up.

A second mechanism is that NAD+-dependent proteins themselves function less effectively as the NAD+ supply shrinks. For instance, the activity of a specific protein that normally slows cellular ageing also falls. This in turn reinforces the accumulation of senescent cells, which fans the flames of inflammation further. It is therefore a self-reinforcing downward spiral.

The declining NAD+ levels are linked in animal research to cognitive decline, muscle loss, metabolic problems and general frailty. Whether that causal link holds just as tightly in humans has not yet been proven. In humans, the evidence so far consists of statistical associations. Animal research shows that restoring NAD+ levels, for example through supplements such as NMN, can slow ageing-related problems. Whether that works the same way in humans and whether it is safe in the long term is still the subject of ongoing research.