Why NAD+ Declines With Age

From the simplest single-celled organisms to humans, all of life cannot exist without a molecule called nicotinamide adenine dinucleotide (NAD+). This molecule has its hands in many processes necessary for humans — and many organisms examined like yeast, flies, worms, and mice — to live a long and healthy life, let alone just being alive. NAD+ plays a role in all sorts of cellular tasks, including basic yet essential functions like helping electrons bounce around between other molecules to carry out many of the cell’s necessary chemical reactions as well as sensing and regulating metabolism.

Simply put, the available pool of NAD+ in a cell is governed by its generation and consumption. But our supply of NAD+ is not immutable; it doesn’t get perfectly recycled. We need to constantly supply ourselves, typically through our diets, with sources for NAD+. Yet as we age, NAD+ levels appear to drop like a runaway train that can never be caught even if all else, such as our diet, stays the same.

The cost of NAD+ decline comes at a severe price. The decline in NAD+ levels appears to play a crucial role in the development of metabolic dysfunction and age-related diseases. This is why there is a growing emphasis on figuring out ways to boost NAD+ levels.

To optimally intervene in the downward spiral of NAD+ levels, we must understand the mechanisms that lead to cellular NAD+ decrease during aging, particularly whether the decline is mediated primarily by changes in its degradation synthesis, or both. Furthermore, it is critical to understand how specific cellular processes like DNA damage, inflammation, and senescence — the age-related freezing of cell replication — impact cellular NAD+ metabolism during the aging process.