Slow Aging Pathway Associated with Development of Brain Cancer

A metabolic pathway associated with slower aging – known as the NAD+ pathway – has now been implicated in the development of brain cancer. The study – published in the journal, Proceedings of the National Academy of Sciences – found that the NAD+ pathway is upregulated in the most common and aggressive form of brain cancer in adults, glioblastoma.

More than 70 percent of patients with glioblastoma don’t live more than two years after diagnosis. This new study found that patients whose glioblastoma displayed high expression of the NAMPT gene, which is involved in the NAD+ pathway, faced shorter life expectancies.

Further, when NAMPT-overexpressing tumors were implanted into mice, they grew rapidly. When the gene was inhibited, the tumors shrank suggesting that the NAD+ pathway could be a good target for glioblastoma therapies.

However, inhibiting this gene could have negative effects on patient aging. The gene products of the NAMPT gene is nicotinamide mononucleotide (NMN), a compound that has shown efficacy in slowing signs of aging in mice.

“There’s a lot of buzz about taking NAD+ precursors for their anti-aging effects, which is based on a lot of great science,” said Dr. Albert H. Kim, an assistant professor of neurological surgery and the senior author on the paper. “We didn’t directly demonstrate that taking NAD+ precursors makes tumors grow faster, but one implication of our work is that if you want to take anti-aging NAD+ precursors, you might want to keep in mind that we don’t yet understand all the risks.”

Kim and his colleagues found that NAMPT was important in allowing human glioblastoma cells to survive and divide. When NAMPT was inhibited, the glioblastoma cells became sensitive to radiation therapy, which is one of the most common cancer treatments for a variety of forms of the disease.

“If you target the NAD+ pathway, you can disrupt the ability of the cancer stem cells to self-renew, and you can also make them more sensitive to radiation treatment,” said Kim. “In a patient, that could mean that if you suppress the pathway, the same dose of radiation may be more effective at destroying the tumor.”

As the NAD+ pathway is very complex, and not fully understood, Kim cautions against tinkering with the machinery before we can accurately predict the results. A human clinical trial assessing the safety of NMN is currently being conducted in Japan, however the molecule is already being marketed there as an anti-aging supplement.