Who would not want to delay the onset of age-related diseases and live longer? As it turns out, the secret to a longer life is actually quite simple: just consume less food and restrict the amount of calories.
This is the conclusion of a new study by scientists from the US and China that 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 long known, these new results show how this restriction can protect against ageing in cellular pathways. The results of the study have been published in the scientific journal 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," explained Prof Juan Carlos Izpisua Belmonte, a senior author of the new paper and professor at Salk Institute’s gene expression laboratory. "This gives us targets that we may eventually be able to act on with drugs to treat aging in humans."
Statistically, ageing is the highest risk factor for many human diseases, including cancer, dementia, diabetes and metabolic syndrome. Various studies have shown caloric restriction in animal models to be one of the most effective interventions against these age-related diseases. Although researchers know that individual cells undergo many changes as an organism ages, they have not known how caloric restriction might influence these changes.
For the new study, Prof Belmonte and his collaborators—alumni from Salk lab, who are now professors running their own research programmes in China—compared rats that ate 30% fewer calories, with rats on normal diets. The animals’ diets were controlled from age 18 months through 27 months. This would roughly be equivalent to a human following a calorie-restricted diet from the age 50 years through 70.
At the start and the conclusion of the diet, Prof Belmonte’s team isolated and analysed a total of 168,703 cells from 40 cell types in 56 rats. These cells were taken from fat tissues, liver, kidney, aorta, skin, bone marrow, brain and muscle. In each isolated cell, the researchers used single cell genetic-sequencing technology to measure the activity level of genes. They also considered the overall composition of cell types within any given tissue and then compared old and young mice on each diet.
Many of the changes that occurred as rats on the normal diet grew older did not occur in rats on a restricted diet. Even in old age, many of the tissues and cells of animals on the diet closely resembled those of young rats. Overall, 57% of the age-related changes in cell composition seen in the tissues of rats on a normal diet were not present in rats on the 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 corresponding author Prof Guang-Hui Liu, from the Chinese Academy of Sciences.
The researchers found that some of the cells and genes most affected by the diet were related to immunity, inflammation and lipid metabolism. The number of immune cells in nearly every tissue studied dramatically increased as control rats aged; however, it was not affected by age in rats with restricted calories. In brown adipose tissue—a 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 aging could be systematically repressed by caloric restriction," said corresponding author Prof 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," says Prof Concepcion Rodriguez Esteban, another of the research paper's authors and a staff researcher at Salk Institute. "The state of your cells as you age clearly depends on your interactions with your environment, which includes what and how much you eat."
The team is now trying to utilise this information in an effort to discover ageing drug targets and implement strategies towards increasing life and health span.