The History of NAD+ Nicotinamide adenine dinucleotide (NAD+) is considered a critical molecule for human life, given its versatility. It plays an integral role in providing cells with energy; almost all biological processes require NAD. For this reason, Nicotinamide Mononucleotide has become the focus of biological research in recent times. A “factor” that stimulates the fermentation of sugar into alcohol was discovered by William John Young and Arthur Harden in liquid extracted from brewer’s yeast in 1906. This factor was given the name of “co-ferment” at that time and is now known by us as NAD. Harden, with help from Hans von Euler-Chelpin, decided to dig deeper into the topic of fermentation. Having developed an in-depth understanding of NAD, they were awarded with a Nobel Prize in 1929. New developments in NAD studies were also seen in the 1930s under Nobel laureate Otto Warburg, who discovered its part in assisting several biochemical processes. He found that NAD works for electrons as a kind of relay. Biochemical reactions are powered by electron transfer between molecules. Conrad Elvehjem along with his University of Wisconsin colleagues, in 1937, found that NAD+ supplements could treat dogs with pellagra or “Black Tongue.” The symptoms in humans range from diarrhea, mouth sores to dementia. It occurs due to a deficiency of niacin and is treated with nicotinamide, a precursor to Nicotinamide Mononucleotide. Another research that proved to be essential towards understanding NAD+ was Arthur Kornberg’s. Throughout the ’40s and ’50s, his research led him to discover RNA transcription and DNA replication principles. In 1958, Philip Handler and Jack Preiss found the biochemical stages involved converting nicotinic acid into NAD. These steps are now known as “Preiss-Handler Pathway”. Mandel, Weill, and Chambon, in 1963, found that Nicotinamide Mononucleotide activates a vital nuclear enzyme by creating the cellular energy needed by it. This finding formed the basis for a further string of discoveries on a kind of protein known as PARP. This protein plays a crucial role in cell death regulation and repairing DNA damage. Its activity is also linked to changes in lifespan. Soon in the year 1976, Rechsteiner and his fellow scientists stumbled upon convincing evidence that suggested NAD+ to have “other major functions” in cells of mammals, something more than its traditional role of an energy providing coenzyme. Nicotinamide Adenine Dinucleotide or NAD+ is a coenzyme necessary for fundamental cellular function. Natural catalysts called enzymes use the coenzyme as helper molecules to enable themselves to function normally What Function Does NAD+ Perform? Nicotinamide Adenine Dinucleotide, after water, is the most prevalent molecule in the human body. Hence, you cannot overstate its importance. Proteins like the sirtuins use this to fix damages in DNA. NAD+ is also essential for mitochondria which synthesize energy on the cellular level to be used by the body. Role of NAD+ In Mitochondria as A Coenzyme Inside mitochondria, the powerhouse of the cell, NAD+ has a vital role in cell function. Metabolic processes like the Krebs Cycle, the electron transport chain, and glycolysis, all require its active participation to occur. As a coenzyme, Nicotinamide Adenine Dinucleotide possesses the ability to alter enzyme activity, cell signaling, and gene expression. As it binds to enzymes, NAD+ is involved in metabolism by transferring electrons from molecule to molecule. You can think of this transferring of electrons as the recharging of a battery. As the electrons use up their energy, the battery starts losing its charge. Once expended, these electrons need a little energy boost to get back to their starting position—the NAD+ acts like this booster inside our cells. DNA Repairing With NAD+ The current aging theory suggests that DNA damage is the primary cause of aging. DNA damage is unavoidable; many stressors in our environment, such as pollution and radiation, impair the accurate replication of DNA. The cells in our bodies are equipped with the molecular machinery to take care of this DNA damage. However, as this process uses up the Nicotinamide Adenine Dinucleotide coenzyme and energy molecules, it depletes a good amount of the cell’s valuable reserves. As we age, our bodies produce more PARP or Poly (ADP-ribose) polymerase, a critical DNA repairing protein. This increased level of PARP causes a reduction in the level of NAD+ over time. If the amount of the coenzyme is not restored in the body, it hinders DNA damage repair. The current aging theory suggests that DNA damage is the primary cause of aging. DNA damage is unavoidable; many stressors in our environment, such as pollution and radiation, impair the accurate replication of DNA. The cells in our bodies are equipped with the molecular machinery to take care of this DNA damage. However, as this process uses up the Nicotinamide Adenine Dinucleotide coenzyme and energy molecules, it depletes a good amount of the cell’s valuable reserves. As we age, our bodies produce more PARP or Poly (ADP-ribose) polymerase, a critical DNA repairing protein. This increased level of PARP causes a reduction in the level of NAD+ over time. If the amount of the coenzyme is not restored in the body, it hinders DNA damage repair. What Is the Effect of NAD+ on Sirtuins? Sirtuins are newly-discovered enzymes that help cells with damage repair as well as a timely stress response. These enzymes also contribute to insulin secretion and diseases relating to aging such as diabetes and neurodegenerative problems. Because of their role in cellular well-being, they are popularly known as the “longevity genes” and also as the “guardian of genes.” NAD+ activates sirtuins. David Sinclair, a Harvard NAD researcher and geneticist, explains that the levels of Nicotinamide Adenine Dinucleotide steadily decline in the body with age, which causes a reduction in sirtuin activity. That’s why in old age, our bodies become susceptible to multiple diseases that aren’t present in younger individuals due to the lack of proper DNA and cellular damage repair. The only way to prevent this from happening is to naturally lift up the levels of NAD+ in the body to stop or, in some cases, even reverse the process and signs of aging. How Is NAD+ Synthesized in The Human Body? Human beings synthesize Nicotinamide Adenine Dinucleotide by using small components called precursors as raw materials. These are extracted from the food that we eat. The five precursors found in our bodies include tryptophan, nicotinamide, nicotinic acid or niacin, nicotinamide riboside, and lastly nicotinamide mononucleotide. Of these five nicotinamide, niacin, and nicotinamide riboside are all types of vitamins B3. Numerous biochemical pathways are available in our bodies for synthesizing NAD+; all of these result in the same end product. First up is the De novo pathway, which roughly translates as “from scratch” in English. Starting with tryptophan, the first NAD+ precursor, the pathway moves its way up. Next comes the salvage pathway. To stop proteins from reaching concerningly high levels, the body degrades them all from time to time. During this process of protein degradation, enzymes use a few of these degradation products to fuel new protein synthesis. Therefore, this pathway salvages products formed during Nicotinamide Adenine Dinucleotide degradation to make new molecules of the enzyme. What’s The Best Way to Boost Your NAD+ Level? There are numerous ways to increase levels of NAD+ in the body. The practice of calorie restriction and fasting has proven to raise levels of NAD+ and sirtuin. Studies on mice have shown that reduced calorie intake causes a slowing down effect on the ageing process due to higher levels of the coenzyme. Nutritional coenzymes can be obtained from food, but often the concentration is too low. But you can compensate for this deficiency by taking NMN, which has shown to enhance Nicotinamide Adenine Dinucleotide levels.