While healthcare has dramatically extended our lifespans by preventing certain causes of death, aging still inevitably takes its fatal toll. And, as scientists report in a new Proceedings of the National Academy of Sciences study, that’s not going to change: Whether it’s by cancer or run-of-the-mill cell destruction, aging and death is mathematically inescapable.

In the paper published Monday, Joanna Masel, Ph.D., and Paul Nelson, Ph.D., both of the Department of Ecology and Evolutionary Biology at the University of Arizona, provide mathematical evidence that aging and eventual death must happen, no matter how we intervene in the aging process.

They explain that every cell in the body is tasked with two opposing missions: ensuring its own survival and supporting the organism it’s a part of. Masel and Nelson reason that this endless push and pull between those missions means that aging is unstoppable.

“If you have [no competition] or too little, then damaged cells accumulate and you get senescence,” Masel tells Inverse. “And if you have more than zero, then you get cancer. Either way, you get decreasing vitality with age.”

If we don't die of disease, we will probably die of aging or cancer.

The team came to this conclusion by creating a mathematical model of cell competition within an organism. Cells in a human body, they explain, face a unique set of forces under the dynamic of competition: On one hand, cells need to work together for the body to function properly. But on the other hand, those cells must compete with each other for survival, and natural selection among those cells means that competition allows only the fittest cells to survive. This competition, the authors explain, results in cancer as the cells that inevitably find ways to game the system are the ones that end up growing uncontrollably.

When a human ages normally, the survival of any individual cell is sacrificed in the name of the organism’s health. In other words, a certain portion of each cell’s output is devoted to collective health instead of individual health. Ultimately, the triumph of cooperation over competition means that bodies accumulate dead or dying cells in a way that eventually leads to what we know as aging.

Natural selection is a process that’s more commonly liked with the genetic evolution of a population of individuals than of cells, but previous research has shown it plays a role in aging too as the cells in your body need to survive and work together in order for a person to live. Nelson, a postdoc in Masel’s lab, says the new research makes an even stronger statement about how the process of natural selection affects human aging.

“Even if selection were perfect, we would still get aging because the cells in our body are evolving all the time,” says Nelson.

Small cell lung carcinoma, chromogranin immunostain
Cancer cells are those that "win" natural selection within the body because of their ability to proliferate unstoppably.

Thinking of human body cells in terms of natural selection may make it sound like a good idea to limit weaker cells that will contribute to a body’s decline. But this is more complicated than it sounds, because culling sluggish cells in the name of competitive advantage could create room for undying cancer cells to gain a foothold.

“As soon as there’s an opportunity for some cells to do better than others, there’s an opportunity for them to game that system and become cancer,” says Masel.

Nelson conceived this research while pursuing a different project, one that was looking at similar ideas of the role of selection in aging. Originally, he was working on developing a model to explain how gene regulation in cells might change over time due to aging. In the course of his research, he began looking for models of cell competition as it relates to aging.

“I didn’t find any that looked like what I was looking for, so I set this up,” Nelson says regarding the PNAS paper. “I noticed that the change over time is always negative. Once you put cancer and cell sluggishness together and put in cell competition, you get the conclusion that cell function will always get worse over time.”

In other words, no matter which way cell competition gets balanced, you’ll inevitably either end up with cancer cells or sluggish, poorly functioning cells over time.

“That was an unexpected outcome,” he says. “I didn’t set out to show that.”

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