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Half-way around the world beneath the surface of eastern Africa there exists a small, hairless, and almost blind species of rodent called naked mole rats. These wrinkly, loose-skinned critters have a highly unusual social structure normally associated with insects and found in just one other mammalian species. A queen mole rat gives birth to all of the colony's pups while workers bring her food, dig tunnels, and ward off snakes. Nevertheless, these bizarre creatures have another unusual characteristic which is that not one naked mole rat has ever been observed to have cancer. Researchers from the University of Rochester and Vanderbilt University set out to explain this curious phenomenon and their discovery may prove useful for cancer prevention techniques.
In general, mammals have an anti-cancer defense called contact inhibition. This mechanism stops cell division when the cell density reaches a certain point. Cancer occurs due to the contact inhibition system malfunctioning, thus allowing cells to proliferate uncontrollably. The p27 gene found in humans and common lab mice is responsible for contact inhibition. What makes mole rats even more intriguing is that the researchers could not induce a tumor even after mutating the naked mole rat's cells so that p27 was turned off.
There is another gene that regulates contact inhibition (gene p16) that is essentially non-functional in humans and lab mice. However, in naked mole rats this gene provides another barrier to carcinogenesis termed by the researchers "early contact inhibition". It is called "early" because the p16 checkpoint is the first in a two-tiered cancer prevention safeguard along with p27. Researchers observed the tenacity of p16 when they attempted to render it inoperative. Two aspects of the gene must be shut down, closing one or the other will not affect its functionality. And, of course, in the unlikely event both pathways are rendered inoperative, the p27 gene steps up to block tumor formation.
Furthermore, cultured naked mole rat cells stop dividing once they make contact with another cell. In stark contrast to a single layer of human cells, naked mole rat cells form a monolayer containing just one-third the amount of cells. Clearly, naked mole rats have a hypersensitivity to contact inhibition affording them a determined ability to ward off cancer. If a method to express p16 in humans in the same way as naked mole rats can be found, then we will have a viable treatment of cancer using our own genes.
In addition, naked mole rats age little until the very end of their lives. This is a result of the full expression of the enzyme telomerase. When DNA replicates, some nucleotides at the end of each strand are lost causing progressively shorter DNA as we grow. Eventually, important genes are not replicated and our body begins to break down. Telomerase enables the placement of nucleotides at the end of DNA that can be lost without having any negative effect. Which means cells can grow and divide indefinitely, potentially giving rise to a tumor. In humans, telomerase is suppressed which reduces the risk of cancer but at the same time causes us to age. The safeguards of early contact inhibition on p16 and contact inhibition on p27 mean naked mole rats need not suppress telomerase to stave off cancer and therefore age slowly. This explains their lifespan, which is two-and-a-half decades longer than the average lab mouse. Here too, in the field of age research, the study of naked mole rat DNA proves enlightening.
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