What Is NAD+? Unraveling the Secrets of this Vital Molecule

It has always fascinated humans to stay young and live longer. Even today, many pharmaceutical companies spend millions of dollars finding anti-aging solutions. And we finally do have a compound, which can be a game changer. 

According to recent studies, NAD+ can naturally relieve aging-related symptoms. That is why many anti-aging supplements, including NMN and NR, boost NAD+ to reverse age-associated signs. 

So, have we found the fountain of youth? Or is this just hype created to get attention and money? In this article, I will explore more on this compound, starting with: what is NAD+? How your body produced it, and how you can improve its levels. 

What is NAD+?

Since its discovery, scientists have been investigating NAD+'s role in longevity and improving health. Nicotinamide adenine dinucleotide (NAD) is an important coenzyme that enhances the catalytic activities of several enzymes. 

Found in every cell in your body, NAD+ promotes metabolism, energy production, and regulation of other cellular functions. A powerful oxidizer that accepts electrons and reduces to NADH—another crucial molecule that regulates various cellular reactions.  

Here are some of the key cellular activities that are dependent on NAD+:

• Protein Function Regulation: By regulating the functions of some proteins like sirtuin, it helps maintain optimum metabolic activity and age-related changes.
• DNA repair: Another important aspect that these co-enzymes control is DNA repair. The Poly (ADP-ribose) Polymerases (PARPs) family of proteins is responsible for DNA repair, RNA/protein translation, and DNA integrity. NAD+ is essential for PARPs' regular activity.
• Control Biological Pathways: NAD+ controls various biological pathways, including calcium signaling, metabolism, immune responses, and brain function, with the help of a NAD-dependent enzyme called ADPR-cyclases.

During cellular respiration, energy is converted into ATP, which facilitates electron transfer by NADPH. Later, NADPH is oxidized to form NAD+ in mitochondria. Various cellular pathways are involved in the biosynthesis of NAD+, which we have discussed in the next section. 

How NAD+ is Produced in the Body

NAD+ is synthesized in our cells through multiple pathways, each utilizing different precursors and enzymes. Understanding these pathways provides insight into how our bodies produce this vital molecule:

De Novo Synthesis

The de novo synthesis pathway produces NAD+ from the amino acid tryptophan. This pathway consists of several enzymatic steps, eventually converting tryptophan into NAD+. Although the de novo synthesis pathway is relatively inefficient and slow, it plays a crucial role in maintaining basal NAD+ levels in the body.

Preiss-Handler Pathway

The Preiss-Handler pathway synthesizes NAD+ from nicotinic acid (NA), a form of vitamin B3. In this pathway, NA is first converted into nicotinic acid mononucleotide (NAMN) by the enzyme nicotinic acid phosphoribosyltransferase (NAPRT). NAMN is then converted into nicotinic acid adenine dinucleotide (NAAD) by the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). Finally, NAAD is converted into NAD+ by the enzyme NAD+ synthetase.

Salvage Pathway

The salvage pathway recycles nicotinamide (NAM), another form of vitamin B3, to produce NAD+. NAM is converted into nicotinamide mononucleotide (NMN) by the enzyme nicotinamide phosphoribosyltransferase (NAMPT). NMN is then converted into NAD+ by NMNAT. This pathway is the primary route for NAD+ synthesis in mammals, as it is highly efficient and rapidly responds to changes in cellular NAD+ levels.

NAD+ Precursors

Our cells can also utilize two well-known NAD+ precursors, nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), to produce NAD+. Both NR and NMN can be taken up by cells and converted into NAD+ through various steps. NR is first converted into NMN by the enzyme nicotinamide riboside kinase (NRK), and then NMN is converted into NAD+ by NMNAT.

So, the body does produce and recycles NAD through various pathways. Then, why do you need NAD+ booster supplements like NMN 9000? 

Here's one explanation: Aging! 

As you age, levels of NAD+ start decreasing over time. Studies indicate that by incorporating NAD supplements, one can reduce the symptoms of aging— more in this article: Does NMN make you look younger?

How NAD+ Works in the Body

NAD+ plays a central role in various cellular processes, ensuring that our bodies function optimally. To provide a deeper understanding of its significance, let's explore the multiple ways NAD+ impacts cellular functions.

Cellular Energy Production

One of the primary roles of NAD+ in our bodies is its involvement in cellular energy production. In redox reactions, it transfers electrons between molecules. In cellular respiration, NAD+ facilitates the conversion of nutrients like glucose, fatty acids, and amino acids into energy (ATP). Cells rely on this energy to function properly.

DNA Repair and Genome Stability

NAD+ is a crucial cofactor for sirtuin enzymes that repair DNA and maintain genome homeostasis against cellular stress. Sirtuins perform NAD+ -dependent deacetylation, which is critical in DNA repair. By maintaining the integrity of the genome, it prevents diseases like cancer and neurological impairments.  

Mitochondrial Function

Mitochondria—the powerhouse of our cells—depend on NAD for proper functioning. In mitochondria, NAD(+) participates in pyruvate dehydrogenase, tricarboxylic acid cycle, and oxidative phosphorylation reactions.

Calcium Signaling and Cell Survival

NAD+ is also involved in the regulation of intracellular calcium levels. Calcium is an essential second messenger, playing a key role in signal transduction and cellular communication. NAD+ influences calcium release from intracellular stores, which in turn regulates processes such as cell survival, differentiation, and proliferation. By modulating calcium signaling, NAD+ contributes to the proper functioning of various cellular processes.

Inflammation and Immune Response

NAD+ plays a role in regulating inflammation and immune response. It influences the activation of specific immune cells, such as macrophages, and modulates the production of inflammatory proteins like cytokines. By doing so, NAD+ helps maintain a balanced immune response, preventing excessive inflammation that can contribute to chronic diseases and age-related disorders.

What Are NAD+ Levels By Age

Our body produces NAD naturally, but its levels may vary from person to person. The level of NAD+ gradually decreases as we age, but other factors such as genetics, diet, and lifestyle can also be responsible. 

Here is a rough overview of NAD+ levels by age:

• Young adults: NAD+ levels are typically highest in young adults. The reason being it is required to maintain different developmental processes. 
• Middle age: NAD+ levels start declining as you reach middle age due to increased DNA damage, oxidative stress, and the activation of NAD+ -consuming enzymes known as NADases (CD38, CD157, and SARM1).
• Older adults: NAD+ levels are at the minimum levels in older people. Excessive use of NAD+ in cellular processes at this age contributes to its decline.

Why NAD+ Levels Decrease in the Body

Understanding why NAD+ levels decline in our bodies, particularly as we age, is crucial for developing strategies to maintain optimal levels and support overall health. Here are some of the primary factors contributing to the decrease in NAD+ levels:

Age-Related Decline

As we age, our bodies undergo numerous physiological changes, one of which is the natural decline in NAD+ levels. Research suggests that the expression of genes and enzymes involved in NAD+ synthesis may decrease with age, leading to reduced production of this essential molecule. This age-related decline in NAD+ levels is associated with a diminished capacity for cellular repair, energy production, and immune function.

DNA Damage and Oxidative Stress

Our cells are constantly exposed to various sources of DNA damage, such as environmental toxins, radiation, and normal metabolic processes. This damage can lead to the activation of DNA repair enzymes, including poly(ADP-ribose) polymerases (PARPs), which consume NAD+ as a substrate. An increase in DNA damage and the subsequent activation of PARPs can deplete cellular NAD+ levels.

Additionally, oxidative stress – the imbalance between reactive oxygen species (ROS) production and antioxidant defenses – can negatively impact NAD+ levels. ROS can directly damage cellular components, including NAD+, and trigger cellular responses that consume NAD+ to counteract the damage.

Activation of NAD+-Consuming Enzymes

Apart from PARPs, other enzymes in our cells can also consume NAD+ and contribute to its depletion. CD38, an enzyme involved in immune response and calcium signaling, is one such example. CD38 levels have been found to increase with age, leading to higher consumption of NAD+ and a subsequent decline in its levels.

Metabolic Dysregulation

Metabolic disorders, such as obesity and type 2 diabetes, can have a negative impact on NAD+ levels. These conditions are often associated with increased oxidative stress, inflammation, and mitochondrial dysfunction, all of which can contribute to a decline in NAD+ levels. Furthermore, poor diet and lifestyle choices that lead to metabolic dysregulation can also impair the synthesis and recycling of NAD+.

What Happens When NAD+ Levels Are Reduced?

Reduced NAD+ levels can have various consequences on our overall health, as they can affect numerous cellular processes and functions. 

Impaired Cellular Communication

Several proteins, including sirtuins, are activated by NAD+ in cellular communication pathways. Reduced NAD+ levels affect the function of these proteins, resulting in the onset of age-related symptoms. 

Reduced Stress Resistance

NAD+ has a role in helping our cells resist various stressors, such as heat, toxins, and oxidative stress. When NAD+ levels are reduced, our cells become more vulnerable to these stressors, which can lead to cellular damage and dysfunction. 

Altered Metabolism

Reduced NAD+ levels can impact metabolic processes within our cells, resulting in a decrease in energy production. This can result in fatigue and reduced physical performance. 

Compromised Immune Function

As NAD+ is involved in immune regulation and inflammation, reduced levels can negatively impact immune function. This may result in a less effective response to infections and a higher susceptibility to chronic inflammatory conditions, which can contribute to the development of various diseases.

Cognitive Decline

Brain NAD+ levels can also affect cognitive function, as it is crucial for maintaining neuronal health. The reduced levels may result in impaired neuronal function. It can lead to cognitive decline, memory loss, and an increased risk of neurodegenerative diseases such as Alzheimer's and Parkinson's.

How NAD+ is Powerful and How You Can Get More of It

Understanding the power of NAD+ is essential, as it holds the key to improved health and longevity. To boost your NAD+ levels, you can focus on a few lifestyle changes. These include consuming a balanced diet rich in vitamin B3, regular exercise, and getting adequate sleep. Some people also opt for NAD+ supplements or intravenous NAD+ infusions for a more direct approach.

Does NAD+ Supplementation Increase Lifespan?

While the idea of NAD+ supplementation increasing lifespan is appealing, the research is still ongoing. Some animal studies have shown promising results, but there is no definitive evidence in humans yet. However, maintaining healthy NAD+ levels is undoubtedly beneficial for overall health and well-being.

Final Thoughts

NAD+ is a powerful molecule with a significant impact on cellular metabolism, energy production, and aging. By understanding its role and taking steps to maintain optimal levels, you can support your body in achieving better overall health and potentially slow down aging. Now that you have a grasp of NAD+, you can make informed decisions to optimize your health and well-being.