Diets that restrict caloric intake tend to result in healthier outcomes in mice and people, when it comes to both aging and metabolism. In the extreme, animals have mechanisms for protecting the body when it is starving; tissues and organs will actually atrophy so energy consumption is kept at a minimum. When normal dietary conditions resume, cells can return to their normal state. Scientists wanted to see if such an extreme condition could actually result in a reprogramming of cellular function that would return cells to a state that would allow for cellular regeneration, specifically in pancreatic cells that are ruined in diabetes. This work, published in Cell, along with another study published in Science Translational Medicine, both have only confirmed the findings of many other studies demonstrating the positive health effects of diets that restrict caloric intake.
The scientists observed a positive change resulting from caloric restriction that led to a reversal in diabetes symptoms. A diet mimicking fasting promoted the growth of pancreatic cells that are able to make insulin, which then reduced diabetes symptoms in mouse models of both type I and type II diabetes, as outlined in the above video. A small study in people confirmed positive effects of the special diet when looking at markers for diabetes. The investigators also wanted to learn more about the mechanisms underlying this positive effect.
"Cycles of a fasting-mimicking diet and a normal diet essentially reprogrammed non-insulin-producing cells into insulin-producing cells," said Longo, a Professor of Biological Sciences at the USC Dornsife College of Letters, Arts and Sciences. "By activating the regeneration of pancreatic cells, we were able to rescue mice from late-stage type 1 and type 2 diabetes. We also reactivated insulin production in human pancreatic cells from type 1 diabetes patients."
The scientists determined that in cells modeling type I diabetes, fasting-like conditions resulted in an increase in the levels of a protein called Ngn3, which promoted the growth of cells that make insulin. Because diabetes results from an inability to manage glucose levels due to a lack of insulin or an inability to properly respond to it, the diabetes was ameliorated when insulin production from functional cells was restored.
"These findings warrant a larger FDA trial on the use of the fasting-mimicking diet to treat human diabetes patients to help them produce normal levels of insulin while improving insulin function. Hopefully, people with diabetes could one day be treated with an FDA-approved fasting-mimicking diet for a few days each month and gain control over their insulin production and blood sugar," Longo concluded.
The work reported in Science Translational Medicine highlights how diets mimicking fasting reduce the risk of many disorders associated with aging such as heart disease, cancer and diabetes. There is a large clinical trial now being planned to follow up on this work.