New study from 'NMN' extends lifespan of ALS mice?

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"Feeding NMN to ALS mice extends their lifespan by about 3.5%.

The onset of motor dysfunction is delayed and signal transmission from nerves to muscles is preserved."

0. Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis ( ALS ) is a neurodegenerative disease characterized by the degeneration of motor neurons in the motor cortex of the brain and spinal cord. Commonly known as Lou Gehrig's disease, ALS patients experience muscle weakness and limb atrophy, ultimately leading to paralysis and death.

1. Extending the lifespan of ALS mice

As reported in the journal 'Experimental Neurology,' researchers at the University of Missouri conducted animal experiments to support their finding that NMN supplementation extends lifespan in mice modeling amyotrophic lateral sclerosis .

Graph 1 - C. Difference in survival rate (%) of ALS mice depending on NMN treatment

Graph 1 - D. Average lifespan (days) of ALS mice treated with or without NMN 

Half of the ALS mice fed NMN (400 mg/kg) lived five days longer than the mice that were not fed NMN, which means that their lifespan increased by about 3.5% on average . When converted to human lifespan, this is equivalent to approximately a six-month increase in lifespan. Furthermore, we can see that the ALS mice fed NMN died two weeks later than the mice that did not eat anything . This result is also equivalent to about one year in human lifespan. Although the increased lifespan may not seem long, considering that most ALS patients survive for about two to five years, it is by no means short.

2. Delayed motor dysfunction in ALS mice

A key feature of ALS is the progressive decline in motor function. Therefore, various motor tests were performed to determine whether NMN is beneficial for motor function .

Graph 2 - Rotarod test results (s) according to F. NMN treatment

Graph 2 - Hanging wire test results (s) with and without G. NMN treatment 

The Rotarod test was performed on normal rats, ALS rats, and NMN-administered ALS rats, and the time it took for the experimental groups to fall from the Rotarod was measured . The Hanging Wire Test was also performed, and the time each rat spent hanging on the wire was also measured.

* Rotarod test: A performance test based on a rotating rod with forced exercise activity, generally used to evaluate the exercise performance of rodents, which can measure parameters such as riding time and endurance.

ALS mice fed NMN showed a two-week delay in motor dysfunction . The ALS + NMN mice were able to perform tasks such as jumping on a rotating bar and hanging from a wire more than the ALS mice. Considering that ALS patients often have difficulty controlling their movements, these findings suggest that NMN could potentially delay motor dysfunction .

3. Electrical signal transmission between muscles and nerves in ALS mice

ALS is a disease that affects skeletal muscles by disrupting nerve transmission at the neuromuscular junction (NMJ). We conducted an experiment to determine how NMN administration affects the NMJ .

* NMJ (Neuromuscular junction): The synaptic connection between the terminal of a motor nerve and a muscle, where action potentials are transmitted from the nerve to the muscle.

Graph 3 - B. 10Hz EPP amplitude (mV) with or without NMN treatment

Graph 3 - C. 20Hz EPP amplitude (mV) with or without NMN treatment 

Graph 3 - D. 50Hz EPP amplitude (mV) with or without NMN treatment

Graph 3 - E. 100Hz EPP amplitude (mV) with and without NMN treatment

Graph 3 - F. 200Hz EPP amplitude (mV) with and without NMN treatment

Semitendinosus muscles were extracted from 18-week-old WT (normal mice), ALS mice, and ALS + NMN mice , and EPP responses were recorded at various frequencies (10, 20, 50, 100, and 200 Hz) . The amplitudes for the first five and last five responses during the first and second stimulations were analyzed.

* Semitendinosus: One of the hamstring muscles located in the back of the thigh

* EPP (End plate potential): Depolarization potential of the end plate formed by acetylcholine released from the synapse

At all frequencies (10, 20, 50, 100, and 200 Hz), the EPP of WT mice was significantly greater than that of ALS and ALS + NMN mice, but the EPP of ALS + NMN mice was greater than that of ALS mice. These results suggest that NMN administration corrected the defect in acetylcholine release at the NMJ in ALS mice .

In conclusion, our results indicate that NMN intake can delay motor impairment, improve NMJ function, and enhance healthy lifespan in ALS mice .

4. Could NMN be the solution for ALS?

The ALS mouse model used in this study is based on a mutation in the SOD1 gene found in a small number of ALS patients. This demonstrates the potential therapeutic potential of NMN, but further studies are needed to determine whether NMN can be applied to other mutations.

[References and Figure Source]

[1] New Study Shows NMN Prolongs the Lifespan of ALS Mice, by Boosting NAD+?

https://www.nmn.com/news/new-study-shows-nmn-prolongs-the-lifespan-of-als-mice-by-boosting-nad

[2] Dietary NMN supplementation enhances motor and NMJ function in ALS

https://www.sciencedirect.com/science/article/pii/S0014488624000244?ref=cra_js_challenge&fr=RR-1

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