Recently, the team of Tingting Fang and Jingyun Yang of West China Hospital of Sichuan University in China published a research paper titled Nicotinamide mononucleotide ameliorates senescence in alveolar epithelial cells in MedComm[1].

1. Abstract

Alveolar epithelial cells (ACEs) gradually senescent as aging, which is one of the main causes of respiratory defense and function decline. Investigating the mechanisms of ACE senescence is important for understanding how the human respiratory system works. NAD+ is reported to reduce during the aging process. Supplementing NAD+ intermediates can activate sirtuin deacylases (SIRT1–SIRT7), which regulates the benefits of exercise and dietary restriction, reduce

the level of intracellular oxidative stress, and improve mitochondrial function, thereby reversing cell senescence. We showed that nicotinamide mononucleotide (NMN) could effectively mitigate age-associated physiological decline in the lung of 8–10 months old C57BL/6 mice and bleomycin-induced pulmonary fibrosis in young mice of 6–8 weeks. Besides, the treatment of primary ACEs with NMN can markedly ameliorate cell senescence phenotype in vitro. These

findings to improve the respiratory system function and reduce the incidence and mortality from respiratory diseases in the elderly are of great significance.

The function of various tissues and organs of the body decreases with aging, accompanied by a decrease in intracellular NAD+, including the lungs. However, whether the reduction of NAD+ mediates the senescence of alveolar cells and whether the supplementation of NMN could alleviate this phenotype had not been reported. We administered NMN to C57/BL6 mice aged 8–10 months at a dosage of 500 mg/kg/day for 2 months. After that, aging indexes of lung tissue were detected. Senescent cells accompanied by a reduced proliferation capacity, mainly due to the increase in expression of cell cycle inhibitor proteins. We found that aging-related cyclic inhibitory proteins were significantly reduced in aging+NMN group by gavage, and aging+NMN group by drinking water compared with the aging group. Therefore, we believe the long-term adding of NMN can be effective in improving lung aging.

2. NMN relieves alveolar cell senescence in aged mice

The function of various tissues and organs of the body decreases with aging, accompanied by a decrease in intracellular NAD+, including the lungs. However, whether the reduction of NAD+ mediates the senescence of alveolar cells and whether the supplementation of NMN could alleviate this phenotype had not been reported. We administered NMN to C57/BL6 mice aged 8–10 months at a dosage of 500 mg/kg/day for 2 months. After that, aging indexes of lung tissue were detected. Senescent cells accompanied by a reduced proliferation capacity, mainly due to the increase in expression of cell cycle inhibitor proteins. We found that aging-related cyclic inhibitory proteins were significantly reduced in aging+NMN group by gavage, and aging+NMN group by drinking water compared with the aging group (Figure 1). Therefore, they believe the long-term adding of NMN can be effective in improving lung aging.

3.They are trying to understand whether NMN can relieve human lung cells from functional decline

They tried to understand whether NMN could alleviate the replication and stress-induced senescence in human ACEs via mice models. They found that both in vivo and in vitro, ACEs of the same passage number were significantly reduced in NMN supplemented and non-supplemented groups. The decreased numbers of cells were not changed by the BLM treatment nor the BLM treatment with NMN addition, senescent ACEs were also significantly reduced. they also found that NMN reduced BLM induced inflammation in mouse lungs. Our data suggested that NMN could effectively alleviate the replication and stress-induced senescence of ACEs in vivo and in vitro. It provides a preventive and therapeutic approach for aging-related chronic lung diseases and lung injury caused by external stimuli in the future.

4. About NMN(β-Nicotinamide Mononucleotide)

NMN has a scientific name of β-nicotinamide mononucleotide and is a derivative of vitamin B3 (nicotinamide) with a molecular weight of 334.221 g/mol. The structure of NMN can be divided into two isomers, α and β, of which only β-NMN is a naturally occurring form with biological activity [2].

NMN itself is a substance naturally produced in humans and organisms. Natural NMN can be obtained from a variety of foods. The content of NMN in some common foods is shown in the figure below. Due to the low content in food, it is difficult for humans to meet their own needs for NMN through diet [3].

In 2013, a research team led by Professor David Sinclair of Harvard Medical School proved through experiments that after a week of oral administration of NMN in 22-month-old mice, NAD+ levels in the body increased, and key biochemical indicators related to mitochondrial homeostasis and muscle function were restored. To the equivalent of 6-month-old young mice, the research results were published in the Cell Journal [4].

The NMN raw material used by Professor David Sinclair was produced by Bontac Bio in 2013. As a major supplier in the NMN industry, Bontac Bio currently has a leading green bio-enzyme catalytic synthesis technology platform. It is the first company in the world to obtain Kosher certification and take the lead in achieving full NMN. A national high-tech enterprise for the industrialization of enzyme catalysis. The company currently has accumulated nearly 150 independently developed enzyme catalysis-related invention patents and international patent applications. It has its own enzyme library and more than 600 strains. It has the research and development capabilities of professional enzyme screening, gene + modification, and enzyme immobilization. The products are in health products, Industrial pharmacy, diagnostic reagents and other fields have been widely used. In 2020, Bontac Biotechnology has achieved an annual output of 1,000 tons of enzyme packages and an annual output of 100 tons of co-enzymes.

REFERENCE

[1] Fang T ,  Yang J ,  Liu L , et al. Nicotinamide mononucleotide ameliorates senescence in alveolar epithelial cells[J]. MedComm, 2021(1).

[2] Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans[J]. Cell, 2004, 117(4): 495- 502.

[3] Mills K F, Yoshida S, Stein L R, et al. Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice[J]. Cell metabolism, 2016, 24(6): 795- 806.

[4] Gomes A P, Price N L, Ling A J Y, et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging[J]. Cell, 2013, 155(7): 1624-1638.