This article aims to provide a comprehensive scientific overview of nicotinamide adenine dinucleotide (NAD+), a crucial molecule in the human body. It delves into what NAD+ is, its discovery and research history, how it combats aging, its other functions, current real - world applications, and future prospects. By synthesizing findings from numerous scientific studies, it offers a clear understanding of the significance of NAD+ in maintaining health and potentially extending lifespan.
1. What is NAD+?
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in all living cells. It exists in two forms: an oxidized form (NAD+) and a reduced form (NADH). Structurally, NAD+ consists of two nucleotides joined together by their phosphate groups. One nucleotide contains an adenine base, and the other contains a nicotinamide base. NAD+ plays a fundamental role in various biological processes, especially in redox reactions.
It acts as an electron carrier, shuttling electrons between different enzymes and molecules in the cell. For example, in cellular respiration, NAD+ accepts electrons and hydrogen ions to form NADH. This conversion is essential for the production of adenosine triphosphate (ATP), the cell's main energy currency. In a study published in "Cell Metabolism", it was shown that in the process of glycolysis and the citric acid cycle, NAD+ is continuously reduced to NADH, which then donates electrons to the electron transport chain to generate ATP. This highlights the central role of NAD+ in energy metabolism within the cell.
2. The Discovery and Research History of NAD+
The discovery of NAD+ dates back to the early 20th century. In 1906, Arthur Harden and William John Young made a significant breakthrough when they discovered a heat - stable factor in yeast extracts that was essential for fermentation. Later, this factor was identified as NAD+. In 1929, Hans Von Euler - Chelpin and Arthur Harden were awarded the Nobel Prize for their work on fermentation, which was closely related to the understanding of NAD+.
Over the years, continuous research has deepened our knowledge of NAD+. In 1936, Otto Heinrich Warburg demonstrated the role of NAD+ in fermentation reactions, showing that its nicotinamide part accepts hydride ions to become NADH, enabling the reaction to proceed. In 1938, Conrad Elvehjem discovered the first vitamin precursor of NAD+, the "anti - black tongue factor". In 1948, Arthur Kornberg discovered the first NAD+ biosynthetic enzyme. In 1958, Jack Preiss and Philip Handler identified the pathway for converting niacin to NAD+. In 2000, the discovery of Sirtuin enzymes, which can break down NAD+ molecules into their components, opened up new research directions. In 2004, Charles Brenner and his colleagues discovered the pathway for converting nicotinamide riboside to NAD+. These series of discoveries have gradually built up our understanding of the biosynthesis, metabolism, and functions of NAD+ at the molecular level.
3. How Does NAD+ Combat Aging?
As people age, the level of NAD+ in the body gradually declines. This decrease is associated with a variety of aging - related phenomena. One of the key ways NAD+ fights aging is through its role in mitochondrial function. Mitochondria are the powerhouses of the cell, responsible for producing ATP. As NAD+ levels decline with age, mitochondrial function in various organs such as the brain, fat tissue, and skeletal muscle deteriorates. However, when NAD+ levels were restored through supplementation with its precursors, mitochondrial function improved. The study showed that increased NAD+ enhanced the activity of mitochondrial enzymes involved in ATP production, leading to more efficient energy generation.
Traditionally, age-related dysfunction has been described at the histological level, but it is now known that these changes result from more specific failures at the cellular level. These key cellular changes are collectively known as the “hallmarks of aging” and designing interventions that target these hallmarks is currently an area of intense research. (Doi: 10.1097/PRS.0000000000009673)
NAD+ also plays a crucial role in DNA repair. Poly (ADP - ribose) polymerases (PARPs), which rely on NAD+, are involved in the repair of damaged DNA. With sufficient NAD+ levels, cells can more effectively repair DNA damage caused by environmental factors or normal metabolic processes. This reduces the risk of mutations and cell senescence. For instance, research published in "Science" showed that in cells with low NAD+ levels, DNA damage accumulated more rapidly, while increasing NAD+ levels activated PARP - mediated DNA repair pathways, maintaining genomic stability and potentially slowing down the aging process.
Figure: Reasons for the decrease of NAD+ in the body during aging (DOI: 10.1016/j.jare.2021.08.003)
In addition, NAD+ is involved in regulating the activity of Sirtuins, a family of proteins related to cell survival and the aging process. Sirtuins require NAD+ as a substrate to function properly. They can deacetylate various proteins, affecting gene expression, metabolism, and cell stress responses. A study on nematodes found that increasing NAD+ levels enhanced Sirtuin activity, leading to an extension of the nematodes' lifespan. This suggests that NAD+ - mediated Sirtuin activation may be a key mechanism in the anti - aging process.
4. What Other Functions Does NAD+ Have?
4.1 Promoting Metabolism
Metabolism refers to the sum of all chemical reactions in the body. Anthony and his research team at the University of California found that NAD+ can effectively improve the slowdown of cell metabolism associated with aging. In an experiment with human cells in vitro, cells treated with NAD+ precursors showed increased metabolic rates. The cells had higher levels of glucose uptake and more efficient utilization of nutrients. This indicates that NAD+ can enhance the body's ability to process and utilize energy, promoting overall metabolic function. It also implies that maintaining sufficient NAD+ levels may help prevent metabolic disorders such as obesity and diabetes, which are often associated with a decline in metabolic function.
4.2 Protecting Heart Health
The heart is one of the most vital organs in the human body, and the level of NAD+ in the body plays a crucial role in maintaining normal heart function. A large number of basic research studies have confirmed the positive effect of NAD+ on heart diseases. The reduction of NAD+ may be related to the pathogenesis of many cardiovascular diseases. In a study on rats with heart failure, researchers found that supplementing NAD+ could improve cardiac function. The rats that received NAD+ supplementation showed increased cardiac output and improved heart muscle contractility. This suggests that NAD+ may be a potential therapeutic target for treating heart failure and other cardiovascular diseases.
4.3 Preventing Cardiovascular and Cerebrovascular Diseases
Research indicates that almost all seven subtypes of sirtuins (SIRT1 - SIRT7) are related to the occurrence of cardiovascular diseases, with SIRT1 being a particularly important target for treating cardiovascular diseases. Since NAD+ is the only substrate for Sirtuins, supplementing the body with NAD+ in a timely manner can fully activate the activity of various Sirtuin subtypes, thereby protecting cardiovascular health and preventing cardiovascular diseases. For example, a clinical trial on humans showed that subjects who took NAD+ precursors for a certain period had improved blood vessel elasticity and reduced levels of inflammatory markers related to cardiovascular diseases. This provides evidence for the role of NAD+ in preventing cardiovascular and cerebrovascular diseases.
5. Real - World Applications and Future Predictions of NAD+
5.1 Real - World Applications
5.1.1 Oral Supplementation
Oral supplementation of NAD+ precursors has become a popular method. A study published in 2023 on oral supplementation reported improvements in the "cardiovascular, metabolic, and physical functions" of participants. These supplements are relatively easy to take, and they can be absorbed by the body and converted into NAD+ through a series of biochemical reactions. However, it should be noted that the long - term effects and optimal dosages of these supplements still need further research.
5.1.2 Exercise
Exercise is a natural way to increase NAD+ levels. The principle is that exercise can activate the NAD+ - synthesizing enzyme NAMPT, turning muscles into "factories" for producing NAD+. A study on athletes found that after a period of regular intense exercise training, the NAD+ levels in their muscle cells increased significantly. This not only shows that exercise can enhance the body's self - production of NAD+ but also implies that maintaining an active lifestyle through exercise can have a positive impact on overall health by increasing NAD+ levels.
5.1.3 Diet and Rhythm
Diet also plays a role in regulating NAD+ levels. Foods rich in NAD+ precursors, such as chicken, fish, milk, and green leafy vegetables (which provide tryptophan and vitamin B3), can help the body synthesize NAD+. Additionally, intermittent fasting has been shown to stimulate metabolic flexibility and promote the natural production of NAD+. A study on a group of people who underwent intermittent fasting for several weeks found that their NAD+ levels increased. Avoiding staying up late is also important because lack of sleep can accelerate the consumption of NAD+. By maintaining a regular diet and rhythm, people can better regulate their NAD+ levels and promote health.
5.2 Future Predictions
In the future, research on NAD+ is likely to continue to expand. With the development of technology, more efficient methods of delivering NAD+ or its precursors may be developed. In addition, as our understanding of the relationship between NAD+ and the human body deepens, it may also be possible to customize NAD+ - based health management plans according to an individual's genetic background and health status, further promoting personalized medicine.
Conclusion
In conclusion, nicotinamide adenine dinucleotide (NAD+) is a remarkable molecule with diverse and essential functions in the human body. Its discovery and the subsequent research have revealed its crucial role in energy metabolism, anti - aging, and various other physiological processes. From promoting metabolism and protecting heart health to potentially preventing cardiovascular and cerebrovascular diseases, NAD+ shows great promise. Current real - world applications, such as oral supplementation, exercise, and dietary adjustments, provide ways for people to maintain or increase their NAD+ levels. Looking to the future, the continuous exploration of NAD+ holds the potential to bring about significant advancements in the fields of medicine and health, offering hope for improved health and an extended lifespan. However, further research is still needed to fully understand its mechanisms and optimize its applications.