Scientific Understanding Of Nicotinamide Mononucleotide And Anti-aging

The current global aging situation is severe and growing rapidly. my country's seventh national census data show that there are 190 million people aged 65 and over, accounting for 13.5% of the total population. Population aging will be the basic national condition of our country's future development. Aging will have a huge impact on every aspect of society. Actively responding to population aging and realizing healthy aging has become an important national strategy for countries all over the world. In recent years, human beings have made great progress in exploring the basic mechanism behind aging and intervening in aging.

Figure 1 Proportion of the global population aged 65 and over (Nadeeshani et al., 2022)

1. NAD+ and aging

A series of energy synthesis and metabolism are going on in the human body all the time to ensure the balance and health of life activities. Nicotinamide adenine dinucleotide (nicotinamide adenine dinucleotide, NAD+), as a coenzyme in the redox reaction process, is an important molecule responsible for energy metabolism. NAD+ directly or indirectly regulates many important cellular functions, including intramitochondrial energy synthesis, DNA damage repair, chromatin remodeling, cellular senescence, and immune cell function. The fundamental physiological processes and functions of these cells are critical for maintaining tissue, metabolic homeostasis, and healthy aging.

Aging is a natural process. As we age, NAD+ levels are gradually depleted in the human body, leading to downregulation of mitochondrial energy synthesis in various organs, including the brain, adipose tissue, skin, liver, skeletal muscle, and pancreas. Decreased NAD+ levels are causally linked to age-related diseases such as cognitive decline, cancer, metabolic disease, sarcopenia, and frailty. Therefore, targeting NAD+ metabolic pathways to increase NAD+ levels may be a potential means to improve aging-related diseases and extend human lifespan and healthspan.

Figure 2 Reasons for NAD+ reduction in the body during aging (Nadeeshani et al., 2022) 

2. NMN participates in NAD+ synthesis

There are three NAD+ synthesis pathways in mammalian cells, namely tryptophan de novo synthesis pathway, salvage pathway and Preiss-Handler pathway, among which the salvage pathway is the most effective main synthesis pathway. Nicotinamide mononucleotide (nicotinamide mononucleotide, NMN) is an intermediate product of the second pathway and participates in the latter two synthetic pathways.

Figure 3 The pathway of NMN involved in NAD+ synthesis in mammalian cells (Nadeeshani et al., 2022)

3. NMN and anti-aging

As the world ages, there is an increasing demand for anti-aging supplements that can prolong life and delay the onset of age-related diseases. In recent years, NMN has attracted great attention from the scientific community and consumers. In theory, NMN, as a precursor for the synthesis of NAD+, can slow down the process of NAD+ depletion with age by increasing the level of NAD+ in the body, so it can be used as an anti-aging health product. Furthermore, mitochondrial decay causes aging, and increased NAD+ levels in the body can reverse mitochondrial decay. The scientific community has carried out extensive research on the anti-aging activity of NMN through cell experiments, animal models and clinical trials. There is evidence that NMN can produce beneficial effects in rodent models and human levels, such as protecting endothelial cells, improving blood supply; improving metabolic dysfunction; and protecting the nervous system. In a randomized double-blind clinical trial in 2021, 25 postmenopausal overweight or obese prediabetic women were treated with oral NMN (250 mg/d) for 10 weeks. Insulin sensitivity. In a similar study in 2023, 36 healthy adults (40-59 years old, 38.9% male) were treated with oral NMN (250 mg/d) for 12 weeks, and the level of serum nicotinamide (NAD+ metabolite) in the treatment group was significantly higher than that in the placebo group Increased, arterial stiffness index tended to decrease, but there was no statistical difference. It is worth noting that some studies have also proposed that NMN accumulation can cause axon degeneration, which is an early symptom of many neurodegenerative diseases. It can be seen that the safety research evidence of NMN still needs to be supplemented.

Figure 4 The mechanism of NMN anti-aging (Nadeeshani et al., 2022)

4. Food sources of NMN

NMN occurs naturally in some vegetables (0.25-1.88 mg/100 g) and fruits (0.26-1.60 mg/100 g), including edamame, cabbage, cucumber, broccoli, tomatoes, mushrooms, and avocado. Raw beef and shrimp also contain small amounts of NMN (0.06-0.42 mg/100 g). NMN in the body is mainly located in red blood cells, and NMN that maintains normal physiological functions can be obtained from daily diet.

Figure 5 Main food sources of NMN

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