The evolutionary view of cancer and aging is that these end points stand in opposition: complex organisms such as mammals evolve to some point of balance between risk of cancer and certainty of accelerated aging. This happens because the mechanisms that suppress cancer also inhibit the necessary regenerative capacity to maintain tissue function: it's largely a matter of how free cells are to divide and multiply, taking into account the increasing levels of damage and mutation with age - which increase the chance of a cancer developing.
In research focused on this balance between aging and cancer, two genes - and the proteins they produce - are especially important: p53 and p16. Both can suppress cancer, but at the cost of accelerated aging:
p16 has been particularly interesting of late because it appears to be a plausible candidate for the cancer immunity observed in naked mole rats:
the mole rat's cells express a gene called p16 that makes the cells 'claustrophobic,' stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed
Unfortunately, as recent research illustrates, making use of this knowledge isn't as easy as just ramping up p16 gene expression in other mammal species:
"I didn't anticipate that increased production of the p16 tumor suppressor protein would so readily promote aging," says Enders, who led the study. "The p16 protein has been previously associated with aging, and we know its expression increases during late stages of aging. But the idea that its expression would be sufficient to generate features of aging was surprising."
Although scientists know that loss of p16 is associated with numerous human tumors, they know much less about the function of p16 in normal cells and tissues. To explore this, Enders' team engineered a strain of mice that enables them to control p16 expression in various tissues and at various times in an animal's lifespan. They quickly found that turning on p16 blocked cell proliferation in normal tissues.
The implications of blocked cell proliferation emerged when they expressed p16 in animals that were not yet fully mature. "They developed features of premature aging," Enders says. "To my knowledge, this is the first model that induces striking characteristics of premature aging where there is no macromolecular damage. The premature aging appears to be the result of blocking cell proliferation."
In this respect, p16 is very similar in behavior to p53. But that in fact means that there is great promise inherent in p16 research: a few years ago, Spanish researchers engineered their way around the aging-cancer balance in mice for p53, producing mice that suffered less cancer and lived 50% longer than normal. Trying a similar approach with p16 sounds very plausible. It is also possible that their work is analogous to the biology of naked mole-rats, animals that manage to live vastly longer than the members of other similarly sized rodent species, and this despite their evolved usage of p16 and apparently complete immunity to cancer. Equally, mole-rats might exhibit yet another completely different configuration of mammalian biology - one that it may soon be possible to reverse engineer and test in mice.
Answers to this sort of speculation still lie in the near future, but research into the biochemistry of p16 and p53 is worth keeping an eye on. Few other methodologies can claim to have extended healthy life in mice by as much as that mentioned above, and, furthermore, somewhere in the biology of these species lies a way to simply turn off cancer.