Prevailing opinion holds that human cells accumulate DNA damage and that eventually this damage catches up with the body in a way that causes cancer. A recent study, lead by a team from a University of Colorado Cancer Center, shows that this prevailing opinion is incomplete. In addition to DNA damage, cancer depends on the slow degradation of tissue that surrounds cancer cells, something that naturally comes with aging.

A investigator interprets that when a person is young, healthy cells are optimized to the surrounding tissue. At that point, any mutation that influences function makes a cell less fit, so cells with mutations are not out-competed by the young, healthy cells. But in the aged landscape, mutations may actually make certain cells better, allowing them to out-compete the normal cells and form tumors.

To effectively monitor it, researchers created mathematical models of this kind of natural selection in hematopoietic or blood cells. The models are used to predict what it exists in the real world by combining several variables, like predicting the weather.

When scientists plugged only mutation variables into the model, the result appeared poor fit. Even if it is believed that mutations would play a role -even a big role , the model would not accurately predict stem cell changes overtime or leukemia development without other factors. So, investigators look not only inside cells, but also outside the cells for the causes of cancer.

They added more variables to the model to account for microenvironmental tissue decline. Suddenly, there was a much better fit. The new model, driven by age-related changes in stem cell fitness and behavior, accurately predicts the point at which a cancer cell might out-compete the normal cells and become a leukemia. Importantly, the model demonstrates that the systemic processes accompanying general tissue decline with age have a crucial power in governing cancer cell fates and the odds of developing cancer.

Scientists point out that natural selection only “cares” about the human body until it passes reproductive age. It means that there is programmed maintenance that takes care of human bodies and keeps them fit until around age 40. At that point, the maintenance program gets lazy. And tissue landscape then starts to change, and unfortunately it changes in ways that allow cancer cells to out-compete normal cells.

In summary, only mutations, although necessary, cannot promote blood cancer development without an age-altered tissue microenvironment. This implies that in addition to research and drug development aimed at the genetic mutations associated with cancer, scientists need to work on maintaining the fitness of  human tissue landscape in order to prevent cancer cells from taking over. Natural selection has provided human bodies with a very effective mechanism to accomplish this maintenance until middle ages.

Reference:

Stochastic modeling indicates that aging and somatic evolution in the hematopoietic system are driven by non-cell-autonomous processes. Aging, December 2014