Life's full of tradeoffs. Splurge on a vacation this year, and you're forced to live frugally next year. The same holds true for cancer and growing old: the very process that guards against tumors early in life may contribute to aging later on.
At the heart of this tradeoff is a cellular response called senescence, a little-understood process in which cells stop dividing. Senescence is nature's way of fighting cancer. It's initiated in damaged cells that are at risk of developing into tumors. If cells can't divide, cancer can't spread. But ever since senescence was first observed 40 years ago, scientists surmised it also contributes to the trappings of old age such as failing eyesight, wrinkling skin, even cancer. The longer we live, the more senescent cells accumulate, and the more tissue breaks down.
But how could something that guards against cancer turn so bad? Judy Campisi has devoted the last fifteen years to exploring this Jekyll and Hyde phenomenon. As a cell biologist in Berkeley Lab's Life Sciences Division, she's at the forefront of understanding the shifting role of senescent cells throughout the lifespan of organisms.
Not surprisingly, her foray into the cellular underpinnings of aging comes by way of cancer research. After receiving a Ph.D. in biochemistry from New York's Stony Brook University, she studied the relationship between cell cycles and cancer at Harvard Medical School. Next, she established her own lab at Boston University and further explored how normal cells become cancerous. She then came to Berkeley Lab in 1990 to focus on what happens to cells after they stop dividing.
She knew that when cells become senescent, they secrete enzymes that degrade nearby tissue. She also knew that some cells, in a completely unrelated process, mutate and become pre-cancerous. Now, she's beginning to learn how these two processes conspire to promote age-related cancer. In young people, both cell mutations and senescence are often harmless because odds are they don't occur near each other. In addition, healthy tissue suppresses the spread of mutated cells.
But as people age, and the prevalence of mutations and senescence increases, a dangerous game of chance develops. If a mutated cell appears next to tissue that's been compromised by a senescent cell, the mutation can spread. This is because damaged tissue can't suppress the growth of mutated cells. So sooner or later, as people age and more and more of their cells either mutate or become senescent, there's a good chance a mutation will occur next to damaged tissue. And when this happens, conditions become ripe for cancer.
That much is known. What isn't known is how a cell first becomes senescent. And how and why do these cells secrete tissue-damaging enzymes? Even more remote, but tantalizing, is the possibility of therapies that fight cancer by reducing the effects of senescent cells.
"In theory, if you can get senescent cells to die, you can retard cancer," Campisi says.
"You'd still have mutations, but you wouldn't have this all-important synergy. Could we develop therapies that eliminate senescent cells, or prevent them from secreting enzymes?"