It's long been clear that cancer is a disease of aging. While children and younger adults are of course afflicted by certain types of the disease, the vast majority of cases occur in people over 50. But from that simple observation, researchers are just beginning to tease out the intricate connections between the biological processes driving both the disease and the aging process. Though the research is in early days, they're discovering how the two may be linked, and even how the forces of evolution may have produced a tradeoff: the ability to protect against cancer at the expense of a faster aging.
Judith Campisi, a research scientist at the Lawrence Berkeley National Laboratory and the Buck Institute for Age Research, sees the relationship two ways. First, she says, the same forces that damage our genes likely drive both cancer and aging. For example, oxidative stress, a type of DNA damage caused by free radicals and other molecules, has been associated with both processes, says Steven Austad, a biologist at the Barshop Institute for Longevity and Aging Studies at the University of Texas Health Science Center. (Austad is also deputy director of research at the American Federation for Aging Research, which funds studies on aging and age-related diseases.) Any biological processes that protect against oxidative stress and other forms of DNA damage are "unequivocal good guys," says Campisi. "They protect against cancer, protect the genome, and protect longevity."
But there's a second, more complex way to view the relationship between aging and cancer. The working hypothesis, explains Campisi, is that "cancer was a problem that evolution had to solve very early on, when an organism evolved the ability to regenerate and repair tissue." Cancer is characterized by cells dividing wildly, with no brakes; if a cell can't divide, it can't become cancerous. One solution that evolved: a whole class of naturally occurring tumor suppressor molecules that can disable cells in danger of going haywire. They do it either by telling the cell to kill itself, through a process called apoptosis, or by simply turning off the potentially dangerous cell's ability to divide, a process called senescence. That process, Campisi says, helps hold off cancer in our reproductive years.
But there's a tradeoff. The problem is that those senescent cells, while they have lost their ability to divide out of control, may trigger inflammation in nearby cells and tissues, and inflammation is linked with a host of age-related disease, including late-life cancers. Experiments in mice show that goosing one important tumor suppressor gene, p53, so it's a little bit activated all the time, does certainly hold off cancer ... but the mice age prematurely. It has been possible to regulate the action of p53 in a kind of Goldilocks mode—not too much, not too little—and that produces mice that are both tumor-free and don't age prematurely, says Campisi. While it sounds great, "that's easy to do in mice, but difficult to do in people," she says. Some other possible tactics include figuring out why the senescent cells are secreting molecules that promote the dangerous inflammation and whether suppressing that secretion would help. Or, she says, maybe there's a way to get rid of the senescent cells entirely.
Another frontier of research involving both aging and cancer: telomeres, the lassolike piece of DNA that protects the end of a chromosome. Over time, as a cell divides, its telomeres get shorter and shorter until each is too short to form a lasso loop. The cell then enters senescence, explains Jack Griffith, a professor of microbiology and immunology at the Lineberger Cancer Center of the University of North Carolina-Chapel Hill. An enzyme called telomerase restores these fraying ends in egg and sperm cells—as well as in most cancer cells. So, why not knock out telomerase in the body in order to fight cancer? Well, about 15 percent of tumors don't depend on telomerase—they use other methods to keep their DNA ends from fraying. And blocking telomerase could mean other cancers switch to that route, too. So there's no easy, universal fix.