Does NAD+ Decline With Age?


Scientists have discovered that our levels of NAD+ decline with age by 50% every 20 years. Low NAD+ levels are a problem because NAD+ plays a vital role in the way our bodies work and we cannot live without it. When levels of NAD+ are low it gets harder for our cells to produce energy, repair DNA and switch-on biomolecular maintenance pathways that protect our cells. If low NAD+ levels persist over time our cells suffer from cumulative damage that leads to many of the symptoms, and negative health consequences, we associate with ageing.


Why does NAD decline with age?

When your body is young it naturally makes and retains high levels of NAD+. But as you age the NAD+ in your body drops significantly. There are two main reasons why NAD+ declines with age.

The first is that cells cannot absorb NAD+ directly from nutrients in our food but have to manufacture it for themselves. The problem here is that old cells are not as good as young cells at manufacturing the NAD+ they need. This is because one of the main enzymes (called NAMPT) that generates most of our NAD+, in a biological process known as the 'NAD salvage pathway', actually declines with age.


Here's how the NAD+ salvage pathway works. When NAD+ is used up by the cells it gets turned into something called nicotinamide. The role of NAMPT is to recycle nicotinamide back into fresh NAD+ using the NAD+ salvage pathway.


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Old cells don't have enough NAMPT to do this efficiently, so nicotinamide doesn't get efficiently recycled back into fresh NAD+. Instead the nicotinamide becomes methylated, gets removed from the cell and is effectively wasted. The net effect over time is a decline in NAD+ levels because old cells are less efficient at recycling their own NAD+.


Secondly, NAD+ is used up much faster in old cells because they have to work harder to fix damage that has accumulated throughout our lives. For example, increased DNA damage in older cells leads to DNA repair enzymes being more active and therefore requiring more NAD+ to do their vital work. Older people also suffer from increased inflammation, which leads to higher levels of the CD38 protein that also uses up great quantities of NAD+.

This imbalance between NAD+ recycling efficiency and rising NAD+ demand explains why our levels of NAD+ decline by around 50% every 20 years. As we age our basic cellular functions have to fight over a dwindling supply of NAD+ that continues to shrink as the years pass.