New research has added to the evidence that suggests that dietary restriction has health benefits. The work, by a lab that has been studying this phenomenon for years, used a rodent model to show that reducing caloric intake can lower inflammation levels in the body. The findings have been reported in Cell.
"We already knew that calorie restriction increases life span, but now we've shown all the changes that occur at a single-cell level to cause that," said the senior author of the report, Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and Roger Guillemin Chair holder. "This gives us targets that we may eventually be able to act on with drugs to treat aging in humans."
According to the National Institutes on Aging, calorie restriction is not just a diet; it involves reducing the caloric intake below what typical for a day without causing malnutrition or nutrient deprivation. Studies in a worm model, C. elegans, as well as in fruit flies have shown that fasting and caloric restriction, respectively, lengthened lifespan. But there is not enough evidence yet from human studied to draw firm conclusions.
We do know that as humans age, they are at greater risk for a wide variety of diseases, and animal studies have suggested that caloric restriction reduces that risk. In this research, the Belmonte lab and scientists that are Belmonte lab alumni now heading their own labs in China controlled the diets of rats from the age of 18 to 27 months, which is supposed to mimic a person's age from 50 to 70. Some rats got a normal diet while others were fed 30 percent fewer calories. The scientists also harvested several tissue types from the rodents at the start and end of that period, including fat, liver, aorta, bone marrow, muscle, and brain tissue.
In this work, 56 rats yielded 168,703 cells that the researchers analyzed using single-cell genetic sequencing tools. They found that the calorie-restricted rodents did not experience many of the changes that the mice fed a normal diet did; around 57 percent of cellular changes related to aging were not observed in rodents that were fed a calorie-restricted diet.
"This approach not only told us the effect of calorie restriction on these cell types but also provided the most complete and detailed study of what happens at a single-cell level during aging," said the co-corresponding study author Guang-Hui Liu, a professor at the Chinese Academy of Sciences.
Genes related to inflammation, immunity, and lipid metabolism were found to be impacted by the change in diet. Immune cell numbers increased as rodents on a normal diet aged, which was not seen in the restricted rats. Anti-inflammatory genes in the brown adipose tissue of old rats on calorie-restricted diet were expressed at levels seen in young rats.
"The primary discovery in the current study is that the increase in the inflammatory response during aging could be systematically repressed by caloric restriction," said the co-corresponding study author Jing Qu, also a professor at the Chinese Academy of Sciences.
"People say that 'you are what you eat,' and we're finding that to be true in lots of ways," added Concepcion Rodriguez Esteban, a study author and a staff researcher at Salk. "The state of your cells as you age clearly depends on your interactions with your environment, which includes what and how much you eat."