November 08, 2021

The Relationship between NMN and DNA Repair, How It’s Done

NMN stands for nicotinamide mononucleotide. NMN is the direct precursor of an essential molecule called nicotinamide adenine dinucleotide (NAD+). Without NMN, there will be insufficient NDA+ in the body. NAD+ is used by many proteins throughout the body, such as the sirtuins, which repair damaged DNA. Almost all cells have the ability to repair DNA damage. This ability consumes NAD+ and energy molecules.
For instance, a protein called PARP (Poly (ADP-ribose) polymerase) is used by cells to repair DNA. This protein relies on NAD+ to function. Thus, a high accumulation of DNA damage in the body triggers increased PARP, which consumes NAD+. With time, this process causes decreased NAD+ concentration coupled with the ageing factor. Research indicates that NMN promotes DNA repair through its NAD+ boosting ability, which provides PARP for the repair process.
In a 2019 study conducted by Mitchell Cancer Institute, University of South Alabama, breast cells were exposed to DNA damaging agents to demonstrate that NAD+ impacts DNA damage and repair processes. The study discovered that NMN supplementation increased NAD+ content in cells and DNA repair operations increased. At the end of the research, NAD+ boosting agents like NMN were recommended as an effective treatment for cancer and DNA damage-related diseases.

Similarities and differences between βNMN and notαNMN

NMN exits in both alpha and beta forms. While the alpha form is identified as nicotinamide ribotide (notαNMN), the beta derivative (βNMN) is the active Nicotinamide mononucleotide naturally occurring in cells. Both molecules act as precursors of an essential molecule for metabolism known as nicotinamide adenine dinucleotide (NAD+).
According to a New Zealand-China Collaboration review, finding on the two molecules indicates that supplementation increases NAD+ levels during ageing with numerous health benefits. A 2008 research by Weill Medical College of Cornell University, USA, also concluded both molecules as a safe and effective method for boosting NAD+ levels.
The chemical formula of βNMN and notαNMN are roughly the same, except βNMN has an added phosphate group. This added phosphate group makes βNMN a larger molecule than notαNMN. Some scientists believe βNMN is too large to cross cellular membranes and must convert to notαNMN before entering cells. Once inside cells, notαNMN is reconverted to βNMN to produce NAD+, which is used to maintain cellular health.

Relationship between Enzyme and Protein PARP1 and SIRT1

Enzymes are catalysts that make biochemical reactions possible. Coenzymes are ‘helper’ molecules that enzymes need in order to function. Both Protein PARP1 and SIRT1 are beneficial DNA-repairing enzymes required for cellular health.  
The PARP family consists of 17 members. PARP1 accounts for more than 90% of cellular PARP activity. It is mainly found in the nucleus and, to a lesser extent, in the cytosol. According to a 2019 peer review involving the Laboratory of Aging Research and Cancer Drug Target, China, PARP1 plays a role in several cellular functions, including DNA repair, the regulation of inflammation and metabolic processes, ageing, and programmed cell death. However, the best-known function of PARP1 is DNA repair. In action, high DNA damage triggers activation of PARP1 to repair DNA. To make this repair possible, PARP1 consumes NAD+ to be able to bind DNA Strand breaks.
SIRT1 on the other hand is a member of the sirtuin family of enzymes, participating in cellular stress responses and damage repair. The SIRT1 enzyme requires NAD+ for activation. They’re also involved in insulin secretion, the ageing processes and ageing-related health conditions, such as neurodegenerative diseases and diabetes.

 Does NMN Intake Protect Against Stroke?

Defective autophagy (which is the inability of the body to clean out damaged cells in order to regenerate newer, healthier cells) is a cause of hypertension-related stroke.
According to a study by the Sapienza University of Rome, NMN reverses autophagy defects and can protect against stroke. This study concluded that defective autophagy induces dysfunction of the cell mitochondria- a primary cause of energy depletion, harmful oxygen-containing molecule buildup (oxidative stress), and inflammation, which are all major determinants of brain injury due to lack of blood flow. 
To find out if NMN reverses autophagy defects and occurrence of spontaneous stroke, the Italian research team administered stroke-prone hypertensive rat models with 250 mg NMN daily. The result recorded an increase in brain NAD+ levels, linked to improvements in autophagy- clearance of damaged mitochondria and mitochondrial function. They also saw an increase in the survival of blood vessel cells in the brains of the stroke-prone rats fed with high salt diets.
These results indicate the NMN protective effect of stimulating autophagy, which contributes to brain health and lowers the risk of stroke.

NMN Role in Endurance Performance of Athletes

NMN supplementation enhances energy production, increases physical endurance by over 50%, and helps with various physiological characteristics like neuron function and insulin sensitivity.
A human study by the Guangzhou Sport University, China shows that NMN taken orally can increase the aerobic capacity i.e. the consumption of oxygen by muscles —of adult runners. In the review, it was also observed that regimented NMN treatment improves the ability of skeletal muscles to utilize oxygen for more efficient energy production during endurance exercise. 
The Chinese research team concluded after administering NMN powder doses between 300, 600, or 1200 mg/day to 48 runners for six weeks. During this time, the participants trained five to six times per week for 40-60 minutes and underwent heart and lung (cardiopulmonary) exercise testing. Final results proved the effect of NMN on aerobic power and muscular energy on athletes compared to runners who didn’t take NMN. In another study by the University of Tokyo, men over age 65 treated with 250 mg per day showed significant improvement in muscle strength and performance. 

Relationship between NAD+ Consuming Enzymes and Aging

Nicotinamide adenine dinucleotide (NAD+) — the essential molecule with key roles in generating cell energy and maintaining DNA integrity — naturally reduces with age. The decline of cell NAD+ levels is linked to many age-related diseases like cardiovascular impairments, metabolic disorders like obesity, and neurodegenerative diseases such as Alzheimer’s disease.
A 2014 joint research by the Washington University School of Medicine, St. Louis and Massachusetts Institute of Technology, Cambridge, suggest that DNA damage caused by ageing is the primary regulator of NAD+ consuming Enzymes in older adults. For example, enzymes called poly ADP-ribose polymerases (PARPs) consume NAD+ to facilitate DNA damage repair and chromosome maintenance. So, acute DNA damage with age can trigger PARP stimulation, which would lead to a sudden drop in cellular NAD+ level. The same pattern applies to other NAD+ consuming enzymes called sirtuins which play critical roles in responses to DNA damage and cellular metabolism.  
In the end, age-related DNA damage corresponds with PARP activation, corresponding with high NAD+ consumption. This leads to the subsequent diminished activity of the sirtuin called SIRT1 since sirtuins must bind to and degrade NAD+ as a co-substrate to function.

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