By Brent Bauer, MD, Mayo Clinic
The human body is made up of 30-40 trillion cells, all of which rely on a coenzyme called nicotinamide adenine dinucleotide (NAD+) to function properly and perform daily functions. Therefore, NAD+ is a key factor in health and well-being, or the lack thereof.
Research shows that NAD+ levels decrease with age. This decline has a major impact on the development of age-related diseases such as diabetes, Alzheimer's disease, obesity, heart disease and loss of muscle tone.
Scientists around the world are studying how increasing NAD+ levels in the body can help with aging. In this way, the aim is to delay the onset of illness and disability and to ensure a healthier and better quality of life.
What is NAD+ and how does it work in the body?
Scientists have known about nicotinamide adenine dinucleotide for at least 100 years. As a coenzyme, or helper molecule, NAD+ binds to other enzymes to help reactions take place at the cellular level. Although the auxiliary molecule may seem insignificant, NAD+ is vital for many functions in the body; without it, the human body would not be able to function properly and life would simply be impossible.
NAD+ has two main roles in the human body:
- Energy creation. NAD+ is the most important element in cellular metabolism, helping to convert food into energy that the body needs to function
- Regulation of cellular processes. As an accessory molecule, NAD+ directly and indirectly affects many cellular functions, including DNA repair, gene expression, and immune system function.
How NAD+ affects aging
NAD+ declines with age, and the main reason for this is twofold. First, as we age, the body begins to produce less and less NAD+. Second, due to inflammation, oxidative stress, and malfunctioning DNA damage, the body depletes NAD+. As a result, many biological processes that depend on NAD+ are altered
Low NAD+ levels are a key aspect of many age-related problems. Depletion of NAD+ disrupts healthy cellular metabolism. This, in turn, leads to the well-known signs of aging - loss of muscle tone, decline in physical capacity, obesity, weakness, etc. NAD+ depletion is also associated with many age-related diseases.
Because NAD+ is so important to cellular function, there aren't many functions in the body that it doesn't affect. Scientists are investigating the link between declining NAD+ and signs of cellular aging. It is these signs that are considered the main cause of aging of the body.
Signs of cellular aging include genomic instability, telomere loss, epigenetic changes, loss of proteostasis (protein stability), impaired nutrient recognition, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.
Don't worry - you don't have to understand what each of these signs mean. The key is to discuss the effects of NAD+ on several characteristics and how increasing NAD+ levels in the body can reduce the damage caused by aging and improve the overall aging process.
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Genomic Instability
Genomic instability means that there are defects in the processes that control cell division. As a result, during cell division, the genome changes and is no longer able to make an exact copy of the original model. When DNA fails to replicate properly or repair existing damage, mutations in the genetic code occur.
Reduced NAD+ levels inhibit the cell's ability to divide and repair DNA. Studies show that supplementing NAD+ levels in aging mice increased the cell's ability to repair damaged DNA.
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Telomere behavior
At the end of each chromosome is a protective cap called a telomere. Telomeres shorten each time a cell divides. When telomeres become too short, cells can no longer reproduce, leading to tissue degeneration and eventually death. Shortened telomeres are associated with many age-related chronic diseases.
Telomere length and function are maintained by a group of proteins called sirtuins. Among many other functions, sirtuins regulate and delay cellular aging and are dependent on NAD+ for proper function. A recent study in mice showed that increasing NAD+ is associated with increased sirtuin activity. Increased activity of sirtuins stabilizes telomeres, reduces DNA damage, and improves the status of telomere-dependent variables.
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Cell aging
Another biological aging process is called cellular senescence. Usually, when aging and damaged cells die, the immune system removes them from the body. However, when we talk about the aging process of cells, we talk about 'zombie cells'. These 'zombie' cells are malfunctioning cells that have stopped dividing, but do not die and remain in the body. With age, they accumulate and contribute to the unfavorable state of the body associated with aging.
Studies have shown that increasing NAD+ levels in aged mice rejuvenated and prevented the aging of muscle stem cells and increased overall lifespan.
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How to increase the amount of NAD+ in the body?
Many healthy lifestyle strategies and habits increase NAD+ levels in the body. NAD+ levels can be increased by adequate physical activity, intermittent fasting, a healthy diet, adequate sleep, and avoidance of physical stressors such as toxins and excessive sunlight.
If age or medical conditions make it difficult to maintain a healthy lifestyle, the next best option is to take supplements such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR). Both are in the form of vitamin B3 (niacin) and are converted to NAD+ in the body.
Laboratory studies in mice show that NMN or NR supplementation improves many physiological functions. One study found that supplementing the drinking water with NMN improved cardiovascular function in older mice. Another study in mice showed that NR can support aging-related cognitive function.
Most of the research on the effects of NAD+ on aging has been done in the laboratory and in small mammals. A twelve-month study in mice showed that NMN supplementation was well tolerated and had no ill effects. However, it should be noted that long-term data on human NMN supplementation is not yet available, so if you are pregnant or breastfeeding, it is best to avoid these supplements.
Aging is a complex cycle of interrelated processes. Increasing the amount of NAD+ in the body is considered one of the potential ways to improve age-related conditions and extend a person's healthy life span. Much research is currently being done to determine whether increasing NAD+ levels will benefit the aging human.
This article was originally published in Thorne