Do Naked Mole Rats Confirm That Senescence is a Cancer Defense?

On page 83 of my 1992 book Cancer Selection I wrote: My theory thus explains the origin and function of [Bilaterian] aging. The programmed shutdown of the cell-renewal process was one of several mechanisms selected to avoid cancer in the earliest [Bilaterians.]

Although The New York Times reported in 2006 that Dr. Norman E. Sharpless of the University of North Carolina reached a similar conclusion (“I don’t think aging is a random process—it’s a program, an anticancer program …”) I am not aware of any published research that would directly confirm or refute this particular part of my theory. But researchers working with naked mole rats may have recently given it some — indirect and tentative — support.

As noted here, here, here and elsewhere these rodents seem to be exceptionally long-lived, with one specimen reaching 28 years. They are exceptional rodents for another reason: they do not get cancer. As reported in 2009 by researchers at the University of Rochester, “a naked mole rat has never been found with tumors of any kind.” More recently (and potentially more significantly) those researchers reported that they have “discovered the chemical that makes naked mole rats cancer-proof.”

So naked mole rats distinguish themselves from other rodents in two ways: they live much longer and they experience zero cancer. In comparison mice live about two years and seem highly susceptible to cancer; a 1962 examination of tumors in randomly gathered wild mice found an incidence of “… 121 neoplasms in 98 animals of a total 225,” an occurrence in forty-four percent of specimens.  (See reference.)

What then is the connection, if any, between the long lives of naked mole rats and their freedom from cancer? A mere coincidence or something more significant?

In Chapter Nine of Cancer Selection I offered a cancer-centered explanation for many fundamental differences between terrestrial vertebrates and terrestrial invertebrates: the vertebrates possess adaptive immune systems capable of killing cancer cells and invertebrates do not. Equipped with that “fail-safe” defense the vertebrate gene pools could produce animals no longer equipped with many preventive defenses against cancer.  In many vertebrate lineages the animals grew larger and lived longer. Larger sizes and longer lifespans required increased mitosis and, given the presence of oncogenes, greater risk of cancer initiation, but, with the presence of the adaptive immune system, no probable long-term increased risk of cancer death. (1)

Not equipped with an adaptive immune system capable of destroying cancer cells, the terrestrial invertebrates depended completely on defenses against cancer initiation. They avoided exposing somatic cells to carcinogenic radiation and eschewed those hallmarks of many vertebrate lineages: increased body sizes and extended lifespans.

If Sharpless and I are correct and Bilaterian senescence is a cancer defense mechanism, did something similar happen with naked mole rats? Did the presence of hyaluronan (HMW-HA), the chemical discovered by the Rochester investigators, reduce the risk of death from cancer to such an extent that it permitted lowering another defense, programmed senescence? Might molecular biologists one day determine that the origin of hyaluronan preceded the mole rats’ extension of lifespan far beyond that of other rodents? (2)

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Reference: Dawes, Clyde J., “Phylogeny and Oncogeny” pp 1-39 in Neoplasms and Related Disorders of Invertebrates and Lower Vertebrate Animals, National Cancer Institute Monograph 31, July 1969 (Dawes, C.J. and Harshbarger, J.C., eds.)

Notes 

1. A complete pdf of Chapter Nine is now available for downloading at www.jamesgraham.bz.

2.  I argue in Chapter Seven of my book that most Bilaterians do not regenerate damaged tissue as flamboyantly as non-Bilaterian multicells. After further thought, I now think that the exceptional regenerating capability of echinoderms may be related to their apparent immunity to cancer. See Starfish Secrets: Did Echinoderms Cure Cancer?

Comments and questions to the author are welcomed here.

At this site you will find links to additional material including my original Letters to the Journal of Theoretical Biology and  the 1992 Nature review of my book.
   

Copyright © 2013, 2014 by James Graham

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