What is NAD⁺?
NAD+, called nicotinamide adenine dinucleotide, is a coenzyme present in all living cells, also known as coenzyme No. 1.
Mitochondria need NAD+ to convert nutrients into energy (ATP). Different physiological activities require different proteins. NAD+ regulates the activity of proteins.
NAD+ has two general and fundamental roles in the human body:
1. Create energy.
NAD+ is key to cellular metabolism, helping to convert food into the energy your body needs to function.
2. Regulation of cellular processes.
As an accessory molecule, NAD+ directly or indirectly affects a variety of cellular functions, including DNA repair, gene expression, and immune function.
What are the causes of NAD deficiency?
● NAD is synthesized by cells from the building blocks (precursors) of NAD contained in the diet. Vitamin B3 (niacin) and tryptophan are the natural building blocks of NAD. Low dietary intake of these precursors is a major risk factor for low NAD levels.
● NAD declines with age, possibly due to a decreased ability to synthesize new NAD and recycle NAD. Lower NAD levels were more likely in middle-aged and older adults, and lower in children.
● NAD is deficient in a high proportion of patients with age-related diseases.
● High levels of NAD-degrading enzymes may be responsible for the rapid turnover and low levels of NAD: Three important enzymes, CD38, PARP, and Sirtuins, have a strong influence on NAD degradation. CD38 is increased in aged immune cells and may be a key risk factor for NAD decline in older adults.
● NAD deficiency appears to be concentrated in some families, suggesting that genetic factors may influence NAD levels, at least partially or in some families.
How does NAD+ affect aging?
The main reason for NAD+ decline with age is twofold. First, as the body ages, it produces less NAD+. Second, damage from inflammation, oxidative stress, and DNA breakdown depletes NAD+ in the body. As a result, many biological processes that depend on NAD+ are altered.
Low NAD+ is a central aspect of many age-related problems. A reduction in NAD+ leads to a decline in healthy cell metabolism. This, in turn, can lead to the familiar signs of aging-loss of muscle tone, decreased exercise capacity, obesity, frailty, and more. Declines in NAD+ have also been linked to many age-related diseases.
Since NAD+ is fundamental to how cells function, there aren't many bodily functions that it doesn't affect. Research is exploring the link between NAD+ decline and hallmarks of cellular aging. These hallmarks are thought to be at the heart of aging in the body.
The cellular hallmarks of aging are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis (protein stability), dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Here's what we know about NAD+'s impact on several hallmarks, and how boosting NAD+ levels in your body can counteract and ameliorate the effects of aging.
1. Genome instability
Genome instability means defects in the processes that control how cells divide. As a result, the genome is altered during cell division and does not exactly replicate the original pattern. When DNA cannot replicate properly or repair damage, it causes mutations in the genetic code.
A decrease in NAD+ inhibits the ability of cells to divide and promote DNA repair. Research shows that supplementing NAD+ in aged mice improves the cells' ability to repair damaged DNA.
2. Telomere wear
Each chromosome ends with a protective cap called a telomere. Every time a cell divides, the telomeres get shorter. When telomeres are too short, cells can no longer reproduce, which leads to tissue degeneration and eventual death. Shortened telomeres are associated with many age-related chronic diseases.
The length and function of telomeres are protected by a family of proteins called Sirtuins. Among their many functions, sirtuins regulate and delay cellular aging-and they depend on NAD+ to function properly. A recent study in mice showed that increasing NAD+ was associated with increased sirtuin activity. Increasing sirtuin activity stabilizes telomeres, reduces DNA damage, and improves telomere-dependent conditions.
3. Cell Senescence
Another biological process of aging is called cellular senescence. Aging literally means "the process of getting older." When old and damaged cells die, your immune system normally clears them from your body. Senescent cells, on the other hand, are malfunctioning cells that have stopped dividing but do not die and remain in the body. They accumulate with age and contribute to the adverse conditions associated with aging.
Research has shown that boosting NAD+ levels in aged mice can rejuvenate muscle stem cells and prevent aging, and increase overall lifespan.
How to increase NAD+ level?
There are currently three main ways to increase NAD+ levels: activation of NAD biosynthetic enzymes and inhibition, NAD+ degradation, NAD+ supplementation, or supplementation
● Ketone bodies increase NAD+ levels
This is also an important principle of longevity / back / back / of the ketogenic diet. Ketone bodies reduce the production of reactive oxygen species in mitochondria by increasing the oxidation of NADH to NAD+. The ketogenic diet promotes NAD+ levels through fatty acid oxidation and glucose restriction. Other studies have found that ketone bodies can increase the redox NAD+/NADH ratio in the resting brain of healthy young adults. Therefore, the state of nutritional ketosis helps to protect the health of the brain, and the ketogenic diet makes your state better and better.
● Caloric restriction (CR)
Caloric restriction is the easiest and cheapest way to increase NAD+, and it has other benefits. There are many ways of caloric restriction to stimulate the increase of NAD+. The fundamental principle is that the calorie reduction reduces ATP, so the body will spontaneously increase some remedial measures. For example, activating the expression of nicotinamide to stimulate the NAD+ salvage pathway, reducing NADH levels indirectly increases the NAD+/NADH ratio, and activates sirtuins. Because NADH is a competitive inhibitor of Sir2, NADH reduces the competition of Sirtuins.
● Foods that boost NAD+
In our daily diet, we can eat more foods that contain NAD+ precursors. For example, tryptophan is found in foods such as turkey, chicken, pork, beef, mutton, and eggs. Vitamin B3, which is more effective than tryptophan, is effective in either form and is abundant in meat, fish and dairy products, especially fatty fish such as salmon, mackerel, sardines and trout. Cheese, yogurt, natto, sauerkraut and other fermented foods are rich in probiotics and B vitamins, which can promote the production of NAD+.
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