A power source for cells
NAD+ is a critical coenzyme present in every living cell. It is involved in a myriad of metabolic processes to help maintain youth at a cellular level.
What is the relationship between NMN and NAD+?
NMN is a potent precursor for NAD+. NAD+ is a critical coenzyme in the human body that regulates DNA damage repair, immune response, gene expression, and metabolism with widely-recognized anti-aging effects.
NAD+ levels in our organs and tissues including the pancreas, fat, skeletal muscles, liver, and brain fall as we grow older.
NMN helps replenish NAD+ levels
NMN is an immediate precursor to NAD+, although uptake pathways of NMN vary with tissue types. It can be dephosphorylated to NR, which enters cells, and converted back to NMN by an enzyme called NRK. It can also be transported directly into cells by a highly-specific transporter SLC12A8.
1、Help slow down aging
Telomeres, which cap the ends of chromosomes, are a kind of molecular clock. With every cell division, they get shorter.
When telomeres reach a critical length the cell will not further undergo cell divisions and become senescent or otherwise dysfunctional, leading to aging.
NAD+ can alleviate telomere dysfunction by restoring Sirtuin (a key factor of longevity) and PARP (a DNA repair enzyme) levels.
Sirtuin (a key longevity factor) and PARP (DNA repair enzyme)
Sirtuin and PARP are critical to almost all pathways to cellular aging. Many studies show that epigenomic regulation of sirtuins and PARP have significant anti-aging effects.
NMN and senescent cells (i.e. “zombie cells”)
When a cell becomes mutated or injured, it often stops dividing and become senescent. Senescent cells excrete a glut of molecules — including cytokines, growth factors and proteases — that affect the function of nearby cells and incite local inflammation. When senescent cells begin to accumulate and the immune system stop responding to them, these secretions can lead to age-related diseases including osteoarthritis and atherosclerosis.
NAD+ metabolism can help remove senescent cells and alleviate chronic diseases related to aging.
2、Improve sleep
A circadian cycle is an internal regulation process which is affected by irregular eating patterns, sleep/wake time, light, and age.
NAD+ can help us improve sleep quality by modulating SIRT1, which regulates our circadian clock gene expression.
How does NMN improve sleep quality?
The susceptibility of our circadian rhythm to external factors is often tangible: it can be easily influenced by our sleep/wake patterns, diet, exposure to light, and age.
However, the impact of disruptions to our circadian rhythm is often not felt immediately. For example, many studies show that sleeping with the lights on will disrupt our circadian rhythm and lead to obesity, myopia, and even growth disorders. However, in the short term, sleeping with the lights on may only lead to a sense of poor sleep quality.
Three pathways that help regulate our circadian cycle
- Positive feedback loop：Activation of circadian transcription by the heterodimeric factor CLOCK-BMAL1
- Negative feedback loop：Inhibition of circadian transcription by Period (PER) and Cryptochrome (CRY) proteins towards CLOCK-BMAL1
- Complex, interconnected processes：The activation and inhibition of the BMAL1 gene
The SIRT1 enzyme connects the NAD+ pathway to the circadian transcription loops to form the NAD+ – SIRT1 – CLOCK:BMAL1 – NAMPT – NAD+ pathway. Through this pathway, NAD+ levels control our circadian rhythm. Hence, intaking the right amount of the NAD+ precursor NMN will help restore our circadian rhythms.
3、Boost energy
Stress is a common phenomenon in today’s society and causes suboptimal health in many people, leading to lack of energy and fatigue.
NAD+ can increase ATP levels by maintaining mitochrondrial fitness to boost our energy.
What is the mitochondria?
Mitochondria generate 95% of the chemical energy needed to power the cell’s biochemical reactions. Chemical energy produced by the mitochondria is stored in a small molecule called adenosine triphosphate (ATP). It also plays a central role in cell growth and apoptosis. Hence, it is called the “powerhouse” of cells.
Mitochondrial dysfunctions will cause a decrease in cell energy levels and disruptions to cell signaling, leading to health issues and aging.
Research shows that 53% of entrepreneurs work more than 12 hours and even up to 16 hours per day, leading to exhaustion and fatigue.
One of the causes of mitochondrial dysfunction is the loss of NAD+. NAD is a central enzyme in the production of ATP during cellular respiration, which is used as energy to power many reactions throughout the body.
In 2012, Shin-ichiro Imai, MD, PhD, a professor of developmental biology and of medicine at Washington University School of Medicine, discussed the close correlation between cellular NAD+ levels and mitochondrial functions in his landmark paper “The dynamic regulation of NAD metabolism in mitochondria.”
As the immediate precursor of NAD+, NMN has been validated by many studies to be able to rapidly increase NAD+ levels in our bodies, thus improving mitochondrial functions.
In 2020, a research team led by the University of Minnesota showed that NMN treatment significantly increased cellular respiration and ATP production.
Researchers discovered that NMN was able to improve mitochondrial functions in the RPE cells, with improvement most significant at 24 hours. This was mostly measured by ATP production.
Studies on NMN/NAD+
In 2011, a research team at the Washington University School of Medicine led by Shin-ichiro Imai, MD, PhD, found that NMN supplementation might be effective in Type 2 diabetes (T2D) patients.
Studies on NMN/NAD+
In 2013, research led by David A. Sinclair, A.O., Ph.D., a professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, showed that declines in mitochondrial functions induced by a decrease in nuclear NAD+ can be reversible.
Regulatory Status of NMN
NMN is approved in Japan as a raw material
NMN is approved by the FDA as an investigational new drug
Combining an advanced drug delivery system
with the highest-grade, 99.9% β-NMN concentrate to create an ultra-premium, new generation NAD+ supplement