'How caloric restriction may slow ageing decoded'

Restricting food-calorie intake may help reduce levels of inflammation throughout the body, delay the onset of age-related diseases, and increase lifespan, according to a study which provides the most detailed report to date of the cellular effects of a calorie-restricted diet in rats.

While the benefits of caloric restriction have been widely studied, the new results, published in the journal Cell, showed how it protects against ageing by shedding light on the chemical processes happening at the cell-level under the diet.

"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 Juan Carlos Izpisua Belmonte, study senior author from the Salk Institute for Biological Studies in the US.

"This gives us targets that we may eventually be able to act on with drugs to treat ageing in humans," Belmonte said.

The researchers said caloric restriction has been shown in animal models to be one of the most effective interventions against age-related diseases like cancer, dementia, and diabetes.

Although scientists know that individual cells undergo many changes as an organism ages, they have not known how caloric restriction might influence these changes, the study noted.

In the current research, Belmonte and his team compared rats which ate 30 per cent fewer calories with those on normal diets.

They said the animals' diets were controlled from age 18 months through 27 months.

Belmonte and his team isolated and analysed a total of 1,68,703 cells from 40 cell types in the 56 rats at both the start and the conclusion of the diet.

These cells came from fat tissues, liver, kidney, aorta, skin, bone marrow, brain and muscle, they said.

The researchers then used single-cell genetic-sequencing technology to measure the activity levels of different genes in each of these cells.

They also assessed the overall composition of cell types within the tissues, and also compared old and young mice on each diet.

According to the study, many of the changes that occurred as rats on the normal diet grew older didn't occur in the rodents on a restricted diet.

The scientists said even in old age, many of the tissues and cells of animals on the diet closely resembled those of young rats.

About 57 per cent of the age-related changes in cell composition seen in the tissues of rats on a normal diet were not present in the rats on the calorie restricted diet, they added.

"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 ageing," said co-corresponding author Guang-Hui Liu from Chinese Academy of Sciences.

Some of the cells and genes most affected by the diet were related to immunity, inflammation, and fat metabolism, the researchers said.

According to the scientists, the number of immune cells in nearly every tissue studied dramatically increased as control rats aged, but was not affected by age in rats with restricted calories.

They said in brown adipose tissue -- one type of fat tissue -- a calorie-restricted diet reverted the expression levels of many anti-inflammatory genes to those seen in young animals.

"The primary discovery in the current study is that the increase in the inflammatory response during ageing could be systematically repressed by caloric restriction" said study co-author Jing Qu from 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," said Concepcion Rodriguez Esteban, another study co-author from the Salk Institute for Biological Sciences.