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But the lowered redox itself was a big surprise, the researchers said.

There are two key pathways of glucose metabolism: glycolysis and oxidation. Glycolysis can be considered akin to chopping down a tree and cutting it into several large pieces, whereas oxidation equates to burning the tree in a bonfire, generating energy. Typically, while cancer cells are rabid users of glucose via the glycolytic pathway, they use less oxidation than healthy cells, because they prefer to divert glycolytic products toward building new cells. This is a phenomenon known as the Warburg effect.

“What we discovered was almost the opposite of the Warburg effect,” said Perry, who is an associate professor of endocrinology and of cellular and molecular physiology. “The mutation that persisted in the skin increased metabolism of glucose through both the glycolytic and oxidative pathways, whereas the mutation that was eliminated increased glucose oxidation despite reduced glycolysis.”

The researchers then continued tracking the progress of the two “tolerated” mutations, one that is typically removed from skin over time and another that remains in the skin but does not lead to disease.

The mutation that is normally eliminated from skin maintained its lower redox ratio, compared with neighboring healthy cells, they found. The mutation that remained in the skin saw its redox ratio increase, “flattening out” in comparison with neighboring, healthy cells said Greco, the Carolyn Walch Slayman Professor of Genetics and of cell biology and dermatology and a Howard Hughes Medical Institute Investigator.

As a final step in their investigation, the researchers treated the animals with mutated cells with the drug Metformin to inhibit the early redox and metabolic changes. The treatment caused a reversal of each mutation’s behavior in the tissue. Mutated cells that had been expanding halted their expansion; mutated cells that were being eliminated from the skin were no longer able to be eliminated efficiently.