The Structure of NAD and its role in Aging
For anyone looking to restore their body’s energy levels, stamina and repair mechanisms as they age, the role of NAD in making an intervention is a significant one. More specifically, it is useful to consider the structure of the NAD molecule and the characteristics this leads to. That’s because NAD’s chemical make-up enables energy production, cellular signaling and the activation of the longevity genes – all essential processes to slow the onset of (or even reverse) the physical signs of aging.
Molecular Structure of NAD
NAD+ stands for Nicotinamide Adenine Dinucleotide. It is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One of these nucleotides contains an adenine and the other contains nicotinamide.
This structure enables one of the essential roles of NAD, its ability to act as an electron carrier. An electron carrier picks up electrons from one molecule and drops them off at another, a bit like a bus picking up people. This process is essential to the cell’s ability to produce energy and NAD is the electron carrier the cell relies on to do this.
It also means that NAD+ can exist as two forms which you will often see referred to as either the oxidized form ready to collect electrons, NAD+, or the reduced form ready to deliver electrons, NADH.
NAD Redox Reactions are essential to Energy Production
The movement of electrons from one molecule to another is known as a redox reaction. Redox reactions are an essential part of the process that converts energy from the food we eat into cellular energy (ATP). This is why NAD is essential for many metabolic pathways.
The way in which the cell creates energy is a very complex process involving lots of enzymes and reactions and NAD+ is essential to the process. The main stages are:
Glycolysis
The citric acid cycle (also called the Krebs Cycle)
The electron transport chain
NAD is involved in every one of these stages. It acts either as an electron donor or acceptor. Ultimately, without NAD+ this crucial energy production would not occur and life would not exist.
A key point to remember is that these redox reactions don’t actually use up NAD, they simply cause NAD to flip between its two forms. This is relevant in the antiaging process because it’s the NAD+ form that activates the longevity genes.
NAD influences Gene Expression
More recently an additional role for NAD+ has emerged. It has been found that the structure of NAD enables it to activate enzymes and, as a result, NAD is a critical regulator of multiple signaling pathways. Many of the enzymes that NAD interacts with are involved in making modifications to proteins that change their activity, generate cell signaling molecules or modify, suppress or initiate transcription. This means that as well as influencing metabolism, NAD+ can also change cellular signaling and gene expression.
During this role, NAD+ is taken up by the enzyme and broken down into niacinamide. This uses the NAD up. This means that the level of intracellular NAD+ is, therefore, directly influenced by the activity of the enzymes that consume NAD+; an increase in the activity of these enzymes causes a decrease in NAD+ levels.
This is important as it partly explains why NAD+ levels decline with age. As the activity of these NAD+ consuming enzymes increase with age, they will use up more NAD+. Two examples of this are
the enzyme PARP1 which works to repair DNA damage
the glycoprotein CD38 which is associated with managing inflammation in the body
NAD activates the Longevity Genes
Furthermore, the structure of NAD+ enables the activation of the longevity genes, sirtuins. Sirtuins regulate many cellular signaling processes associated with increased longevity. These processes are directly dependent on NAD+ availability to perform their function.
Read more about the Sirtuins and their activation.
NAD has a key role in Human Health and Aging
In his 1930 Nobel lecture, Dr Hans von Euler-Chelpin stated that ‘NAD+ is one of the most widespread and biologically important activators within the plant and animal world’. It is now known to be involved in over 500 biological reactions and plays a key role in the regulation of many biological processes. But above all it may help us to live longer, healthier lives.
As we’ve seen, NAD’s role in both redox reactions and as a coenzyme substrate are intimately linked with multiple key effectors of longevity.
Our understanding of NAD+ and its importance in longevity has developed greatly since its discovery in 1906. We now appreciate that NAD+ levels decline with age, so do these critical cellular redox and coenzyme reactions that it is involved in, ultimately resulting in cellular damage, dysfunction and the symptoms of ageing. The good news is that NAD+ decline isn't a one-way street. It can be reversed and doing so can alleviate the associated symptoms of ageing.
Read more about NAD and Aging