#cd38

Why do we talk about NAD+ again? Because it is the most important molecule for life to exist, and our health directly depends on its amount in our body!This post will help you to understand how your body gets NAD+, how it uses it, and why its level decrease with age based on the latest studies and discoveries. Also... It contains practical advice on how to measure, maintain and potentially increase your NAD+ levels, including references to useful products and services. The three recipes below are from the book "The Longevity Diet: Slow Aging, Fight Disease, Optimize Weight" by Dr. Valter Longo; that definitely worth adding to your diet.

How does our body get NAD+?

Just to remind, NAD+ stands for Nicotinamide Adenine Dinucleotide, a crucial coenzyme that can be found in every cell in your body. NAD+ works as a shuttle bus, transferring electrons from one molecule to another within cells to carry out all sorts of reactions and processes. With its molecular counterpart, NADH, this vital molecule participates in various metabolic reactions that generate our cell’s energy. Without sufficient NAD+ levels, our cells wouldn’t be able to generate any energy to survive and carry out their functions. Other functions of NAD+ include regulating our circadian rhythm, which controls our body’s sleep/wake cycle.  Basically, without NAD+, we would be on the fast track to death. In our previous post, we already showed what food sources provide us with NAD+ precursors for its synthesis inside the cells. There are five major precursors and intermediates to synthesize NAD+: tryptophan (Trp), nicotinamide (NAM), nicotinic acid also known as niacin (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN).  NAD+ can be synthesized de novo by the conversion of the amino acid tryptophan (Trp) through multiple enzymatic steps to nicotinic acid mononucleotide (NAMN). This is one of three known pathways to produce NAD+ in a body, called the Kynurenine pathway. You can find more information on how NAD+ is made by this pathway here. NAD+ can also be made by the Preiss–Handler pathway starting from niacin (NA), a form of vitamin B3. It is known for producing flushing when taken in high amounts. Conversion to NAD+ proceeds in several enzymatic steps. NANM is an intermediate in the pathway, so de novo synthesis from tryptophan shares several steps in this pathway to complete NAD+ synthesis. But most of our NAD+ we get from the third pathway,  called the Salvage pathway. This pathway converts nicotinamide (NAM) to NAD+ with nicotinamide mononucleotide (NMN) as an intermediate. Learn more here.

How is NAD+ consumed in the body?

We already know that NAD+ is a vital coenzyme in redox reactions. It is responsible for accepting "high energy" electrons and carrying them ultimately to the electron transport chain, where they are used to synthesize ATP molecules. Why is it important? Because ATP, or adenosine triphosphate, is an important “energy molecule” found in all life forms. ATP captures chemical energy obtained from the breakdown of food molecules and releases it to fuel cellular processes, such as transcription, DNA replication, DNA repair, and many others. NAD+ has a cofactor in the process of ATP synthesis, which is flavin adenine dinucleotide (FAD+).  FAD+ is a coenzyme form of vitamin B2. When these electron-carrier molecules (NAD+ and FAD+) accept the electrons, they are reduced into NADH and FADH2 (redox reactions). These electrons usually come in the form of hydride atoms. Reduced forms are oxidized back to NAD+ and FAD+ during ATP synthesis. So, here, NAD+ is in the cycle. But... NAD+ is also constantly consumed in cells by the action of a number of NAD+ consumers, including sirtuins, PARP enzymes, SARM1, and CD38. Let's go over with each of these enzymes. Learn more here.

Why does NAD+ decline with age?

NAD+ levels decline in many tissues with age, and this decline is believed to contribute to the aging process. Multiple factors can play a role in the decline, including dietary deficiencies for NAD+ precursors, changes in the expression levels of enzymes that transform dietary precursors to NAD+, or changes in the activity of enzymes that break down NAD+ (see above).  Diet-induced metabolic damage is related to increased activity of PARPs and CD38 following increased DNA damage and inflammation, and NAD+ consumption.  A sedentary lifestyle could be enough to decrease mitochondrial amounts in muscles and, consequently, NAD+ levels, even in the absence of a disease state or changes in NAD+-consuming enzyme activities. There is also a suggestion that the synthesis of NAD+ declines with age and fails to compensate for its consumption. The constant degradation of NAD+ by enzymes involved in various cellular processes requires a continuous resupply of it by synthesis from dietary precursors or recycling from NAD+ degradation products. As shown above, NAD+ recycling via the NAM salvage pathway is a fundamental step to restore NAD+ levels after irreversible degradation mediated by the different classes of NAD+-consuming enzymes (Sirtuins, PARPs, CD38, and SARM1). Learn more here.

How to measure NAD+ level?

Learn more here.

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