Image by Michael Zangani
Previous research has suggested the accumulation of cancer-causing mutations is to blame for the increased risk of cancer in the aging population.
But a study published in The Journal of Clinical Investigation tells another story.
Investigators found that, without age-associated inflammation, older mice developed leukemia no faster than young mice.
The study focused primarily on the “ecosystem” of B-cell progenitor pools.
The investigators wanted to determine what allows a population of healthy B-cell progenitors to be replaced over time with a population of cancerous B-cell progenitors.
“We chose to focus on the role of inflammation in the bone marrow—one of the hallmarks of age-associated tissue changes—where these B-cell progenitor pools live,” said study author Curtis Henry, PhD, of the University of Colorado Anschutz Medical Campus in Aurora, Colorado.
He and his colleagues found that inflammation hurts the growth and maintenance of B-progenitor cells, but that’s not all. Cancerous mutations tend to alter cells in ways that help them survive conditions of inflammation in the bone marrow.
“Suddenly, the healthy cells that were the fittest are no longer the most fit,” Dr Henry explained. “Because the tissue changed, cancer cells have a selective advantage.”
The investigators were able to observe this inflammation-driven natural selection in mouse models. The group worked with mice engineered to prevent inflammation and set out to determine how healthy and leukemia-initiated cells would fare in these conditions.
“Basically, without the effects of inflammation, B-cell progenitor pools stayed fit,” Dr Henry said.
And stopping inflammation reduced the ability of cells expressing the oncogene NRAS from taking over the bone marrow niche.
This study suggests that an increase in cancer risk with age may not be inevitable. Instead of simply being a matter of the passage of time, cancer development in aged populations may be partially dependent on inflammation-associated tissue changes.
“Despite the fact that cancer is largely a disease of old age, almost all cancer modeling in mice employs only young mice,” noted study author James DeGregori, PhD, of the University of Colorado Anschutz Medical Campus.
“This is based on the view that finding the genetic mutation that causes cancer should be enough to understand the disease.”
In these studies, the investigators tested both young and old mice. The older mice were more likely to develop leukemia, but only in the presence of age-associated inflammation. If age-associated inflammation was blocked, the older mice were no more likely than young mice to develop leukemia.
The work implies that stopping the effects of inflammation on tissue could stop cancers from forming. However, inflammation can be necessary in some circumstances. So the investigators said more work is needed to understand how to “tune” inflammation in the elderly to maximize its beneficial effects while minimizing negative effects.
“While it’s premature to suggest that people should take medicines to fight inflammation as they age, we believe our results warrant further study into this potential strategy to combat the age-associated increase in cancer risk,” Dr Henry concluded.
