Calorie Restriction — Stressor or Solution?
In 2010, Dr. Simone was studying the cellular effects of stress while working at the National Cancer Institute as an assistant clinical investigator. She was curious about how different types of stress, like radiation therapy or chemotherapy, changed the genetic makeup of cells, and what happened to them on a molecular level. Looking for new ways to induce stress, she started tapering down how much food she gave her cells; she expected that less food would weaken them and increase molecular signatures of stress. Instead, she found something unexpected — the slightly-hungry cells were actually getting stronger while the cancer cells got weaker.
She then tested out this discovery in mice, probing whether the cancer cells, weakened by calorie restriction, were more vulnerable to cancer treatment. She confirmed that starting animals on a calorie-restricted diet during radiation enhanced the therapy in models of breast cancer. Compared to control animals, the mice eating fewer calories had tumors that grew slower and metastasized less, and they ultimately survived longer.
Though it’s a new concept in cancer treatment, the health benefits of calorie restriction have been studied for the better part of a century. As far back as 1935, studies showed that low-calorie diets extended the lifespan of mice, and over the years, these benefits have been shown to hold true in humans, too: People who stick to lower-calorie diets tend to show fewer molecular signs of aging, have lower blood pressure and are less susceptible to diabetes.
According to Dr. Simone, calorie restriction’s benefits in cancer stem from the fact that healthy cells are better equipped to handle fluctuations in nutrition than cancerous cells. While healthy cells can meet their metabolic needs by drawing on different energy reserves, cancer cells have fewer options, meaning they’re more vulnerable.
“Normal cells can almost hibernate, whereas tumor cells can’t deal with the stress of radiation and calorie restriction at the same time,” says Dr. Simone. “Their machinery doesn’t work as well, and they die faster.”
Part of the “machinery” behind calorie restriction’s effects is the IGF-1R pathway — a cascade of cellular reactions responsible for breaking down sugars and helping cells grow. Cancer cells often have an overactive IGF-1R pathway – meaning they burn up lots of sugars and grow quickly – which is partly why cancer develops explosively compared to healthy cells. Restricting calories can hamstring this pathway, and therefore cancer growth. Furthermore, Dr. Simone has shown that cutting calories during radiation treatment in mice also stimulates the immune system, leading to a spike in cancer-fighting cells.
With a solid foundation of evidence that calorie restriction enhanced the effects of cancer treatment in animal models, Dr. Simone wanted to see if the same held true in patients.
