Astronauts’ exposure to weightlessness during spaceflight precipitates bone degradation and proneness to fracture, however, nicotinamide mononucleotide (NMN) restores bone strength in a rat model for space travel.
Following spaceflight, astronauts usually have fragile bones with a higher susceptibility to fracturing, a condition referred to as osteopenia. To counter osteopenia from space’s microgravity, astronauts have used calcium and vitamin D supplementation while engaging in rigorous exercise regimens. Nonetheless, such countermeasures have proven mostly ineffective against osteopenia, so researchers continuously seek new drugs to restore bone density and strength following spaceflight.
Published in Cell Stress & Chaperones, Yang and colleagues from Xi’an Jiaotong University in China show that NMN restores bone mineral density, an indicator of improved bone strength, in a rat model for microgravity in spaceflight. Interestingly, while bone NAD+ levels fell in the microgravity rat model, NMN replenished bone NAD+ in this animal model. NMN also reduced bone levels of a marker for troublesome oxidative stress, malondialdehyde. These findings suggest that NMN restores bone density and NAD+ levels, while abating damaging bone oxidative stress.
To model how spaceflight affects bone, Yang and colleagues utilized a method that National Aeronautics and Space Administration (NASA) researchers use — hindlimb unloading. Using this technique, they hoisted rats by the tail so that their hindlimbs didn’t contact the ground surface. This procedure allowed the researchers to measure how a lack of usage affects bone mineral density, a marker of bone structural strength.
Rats that underwent hindlimb unloading for four weeks displayed significantly less bone mineral density, indicative of ensuing osteopenia and concomitant bone fragility. Interestingly, when NMN was administered through abdominal injections every three days, the rats exhibited restored bone mineral density. These findings suggest that NMN rescues bone from osteopenia during spaceflight.
To explore the subcellular mechanism behind NMN’s effects against osteopenia, Yang and colleagues measured bone NAD+ levels. The spaceflight rat model exhibited significantly reduced bone NAD+, but NMN administration significantly restored bone NAD+ in the model. The findings suggest that NMN’s ability to preserve bone density stems from how it boosts NAD+ levels.
Since troublesome oxidative stress has been linked to bone degradation and osteopenia during spaceflight, Yang and colleagues measured a molecular marker for oxidative stress — malondialdehyde. The research team found that four weeks of hindlimb unloading more than doubled malondialdehyde levels, but NMN abated the malondialdehyde upsurge in the spaceflight model. These results suggest that by increasing NAD+, proteins like sirtuins that use NAD+ to fuel their removal of oxidative stress factors reduce oxidative stress toward normalized levels, which can help preserve bone density.
“Our work demonstrated that NMN supplementation mitigated osteopenia in [hindlimb unloading] rats,” said Yang and colleagues.
According to the findings, NMN preserves bone density, suggesting that it prevents osteopenia, in a rat model for spaceflight microgravity. Moreover, NMN restores bone NAD+, which declines in the spaceflight model. Restoring NAD+ likely enables proteins like sirtuins to lower troublesome oxidative stress, as seen with the data showing NMN reduces the oxidative stress marker, malondialdehyde. As such, NMN’s ability to increase bone NAD+ likely has the effect of lowering oxidative stress to preserve bone density.
Since a strong safety profile has been established for NMN supplementation, the possibility of these results translating to astronauts traveling through space holds promise. The next step for studying NMN’s ability to help astronauts preserve their bones would be to provide the supplement on the International Space Station. Researchers could measure the astronauts’ bone mineral density before takeoff and after returning to find out whether NMN mitigates spaceflight-induced osteopenia.
Model: Wistar rats
Dosage: 500 mg/kg of NMN every three days for four weeks via intragastric injections