Fight Aging!

Evidence suggests that enhanced DNA repair may act to slow the progression of aging. Researchers here note that increased levels of the metabolite guanosine triphosphate (GTP), a building block and energy source used in a variety of ways in the cell, can improve the pace of DNA repair. There are numerous ways by which GTP levels might be upregulated over the long term, but as researchers here note, the opposite is desirable in the case of cancer, in order to impair DNA repair and make cancerous cells more vulnerable to genotoxic therapies.

Researchers have long known that levels of nucleotides like GTP control how fast DNA damage is repaired, which in turn controls sensitivity to therapies. Researchers previously thought that this only happened because nucleotides are the building blocks that form DNA. But these findings uncover an entirely new way that nucleotides control DNA repair. "GTP impacts resistance or sensitivity to treatment not just because it's a building block of DNA, as we previously thought. Instead of only affecting the physical structure of the DNA, it also acts as a signaler. The levels of GTP turn on a signaling pathway and give cells instructions to repair damaged DNA."

"In the future, we'd like to develop therapeutics that leverage the relationship between GTP and DNA damage response, both to make cancer cells more sensitive to chemotherapy and radiation and also to boost GTP levels to protect normal tissue from damage. We knew that depleting GTP might make brain cancers respond better to chemotherapy and radiotherapy. Now these findings show why that's happening." The discovery that GTP acts as a signaler helps explain the biological underpinnings of why focusing on GTP is a worthwhile pursuit and could help researchers figure out which patients will derive the most benefit from GTP modulators in the clinical trial.

Link: https://www.michiganmedicine.org/health-lab/metabolite-tells-cells-whether-repair-dna