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Age-Reversing Metabolite Interests Mars Mission

University of NSW researchers have identified a critical step in the molecular process that allows cells to repair damaged DNA. Their experiments in mice, published in Science, suggest a treatment for DNA damage from ageing and radiation. This has attracted the attention of NASA, which believes the treatment can help its Mars mission.

The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body, mediates the interaction between two enzymes that control a cell’s ability to repair DNA. DBC1 binds to PARP1 outside the nucleus and prevents it from repairing DNA. However, NAD+ breaks up this interaction, enabling PARP1 to fulfil its role in DNA repair.

However, NAD levels decline with age, and hence the ability to repair DNA declines with age. The researchers found that treating old or irradiated mice with the NAD+ “booster” NMN freed up PARP1 to repair DNA. “The cells of the old mice were indistinguishable from the young mice after just 1 week of treatment,” said lead author Prof David Sinclair.

For the past 4 years, Sinclair and Dr Lindsay Wu have been working to make NMN into a drug, with human trials to begin this year at Brigham and Women’s Hospital in Boston. They had already established that NAD+ could be useful for treating various diseases of ageing, female infertility and the side-effects of chemotherapy. “This is the closest we are to a safe and effective anti-ageing drug that’s perhaps only 3–5 years away from being on the market if the trials go well,” Sinclair says.

The work has excited NASA, which is considering how to keep its astronauts healthy during a 4-year mission to Mars. Even on short missions, astronauts experience accelerated ageing from cosmic radiation, and experience muscle weakness, memory loss and other symptoms when they return. On a trip to Mars, the situation will be far worse: 5% of the astronauts’ cells will die and their chances of cancer will approach 100%.

Aircraft passengers are also exposed to cosmic radiation, with a London–Melbourne flight roughly equivalent in radiation exposure to a chest X-ray. In theory, the NMN treatment could mitigate any effects of DNA damage for frequent flyers.

The other group that could benefit from this work is survivors of childhood cancers. Wu says 96% of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, type 2 diabetes, Alzheimer’s disease and cancers unrelated to the original cancer.

“All of this adds up to the fact they have accelerated ageing, which is devastating,” Wu says. “It would be great to do something about that, and we believe we can with this molecule.”