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Scott Lowe thinks senescence might be a cell's strategy to copy with an immediate threat—even if that tactic proves detrimental later on.
The cancer connection seems counterintuitive. Typically, cancer-causing genes spur cells to divide uncontrollably, not grind to a halt. But Lowe's result supports the idea that senescence is a cancer-prevention tactic. Cells must accumulate multiple mutations before turning into full-blown cancer. When a cancer gene turns on, senescence might help cells shut down before additional mutations push the cell to become cancerous. However, shutting down cells to fight cancer could hamper health in other ways. For instance, senescence might deplete the pools of cells that replace damaged ones and keep liver, bone, blood, and other tissues working properly. An accumulation of malfunctioning cells and a loss of new ones to replace them could underlie some of the effects of aging. So is senescence good or bad for the body?
In a sense, cancer and senescence are opposite sides of the same coin. To remain robust, tissues rely on dividing cells for replenishment; yet, left unchecked, cell division leads to cancer. Thus, it might seem a Faustian bargain to guard against cancer now at the expense of decrepit tissues later.
Evolution should favor the anti-cancer mechanism, Lowe says. Genes that improve survival early in life should help ensure that an organism reproduces, and thus the genes tend to be passed down to the next generation. That's true even if the same genes compromise health late in life. “We didn't evolve during a period when we lived 80 years,” says Lowe. “The system isn't built to last that long.”
Some studies on the tumor suppressor gene p53 have supported this idea of a trade-off between cancer and aging. The p53 gene acts as a master controller of anti-cancer mechanisms, including senescence, particularly when DNA incurs damage or telomeres erode. The gene also governs other processes such as a regulated cell death pathway called apoptosis. Several groups of researchers have shown that producing certain forms of p53 dramatically reduces cancer in mice, but those animals age more rapidly than normal.
For decades, cellular senescence was thought to be an oddity seen only in the lab. Few studies provided any evidence that senescence influenced aging or cancer in a living creature. “[Researchers in the] cancer biology field felt it was a cell culture artifact,” says Lowe. “Senescence hadn't been observed in tissues.”
Photo: Zach Seckler \ AP, © HHMI
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