In a study done at Salk Institute, scientists have demonstrated more clearly the cellular effects of caloric restriction as related to aging.
Studies show that aging constitutes the greatest risk for a variety of medical disorders. Metabolic syndrome, diabetes, dementia, and cancer are some of the conditions that tend to be more common among older people.
These diseases are usually the result of increasing levels of inflammation in the body. This, scientists believe, has a connection to diets in part. Calorie-restricted diets have been shown in animal studies to help fight age-related disorders.
However, the current study provides the most in-depth information on how calorie restriction combats aging at the cellular level.
“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,” stated senior study author Juan Carlos Izpisua Belmonte, the Roger Guillemin Chair holder at the Salk Institute for Biological Studies.
The professor said their findings reveal possible targets for anti-aging drugs for humans.
Other researchers Belmonte worked with for the study included three alumni of his Gene Expression Laboratory, who have become professors and also have their research programs.
Their research appeared in the journal Cell.
Fighting aging effects with caloric restriction
For their study, the scientists made use of rats. They placed some of the animals on normal diets and others on diets that had 30 percent lesser calories. The team then compared the rats to see what effects the diets had.
The animals had their diets controlled from 18 months of age until they were 27 months old. According to the researchers, this is comparable to a person maintaining a calorie-restricted diet from 50 years of age through age 70.
To enable them properly examine the effects of diets, Belmonte and his colleagues isolated numerous cells in 56 rats. In total, they analyzed more than 168,700 cells belonging to 40 types of cells.
The researchers obtained these cells from the brain, kidney, liver, muscle, skin, aorta, bone marrow, and fat tissues of the animals. They assessed gene activity levels in each cell as well as overall cell type composition within tissues.
After comparing old and young rats on each diet type, Belmonte and his colleagues found that a lot of the changes that occurred in animals placed on a normal diet did not take place in those on a calorie-restricted diet. The latter group had many cells and tissues that looked a lot like those of young rats in old age.
Animals on calorie restriction showed a 57 percent reduction in age-related effects on cell composition, compared to those on normal diets.
How caloric restriction fights aging
The most interesting part of this study is the demonstration of how a restricted diet can combat the damaging effects of aging.
“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 Jing Qu, a corresponding author and professor at the Chinese Academy of Sciences.
A restricted diet returned the expression of numerous inflammation-fighting genes in brown adipose tissue to the levels it was at a younger age.
A good number of the cells and genes impacted by the diet included those associated with immunity and lipid metabolism. Aging did not have a dramatic effect on the number of immune cells in animals whose diets had lower calories.
A closer look at transcription factors impacted by calorie restriction revealed that a particular one warrants more research. Transcription factors are proteins that turn genes “on” or “off.”
Belmonte and his team observed that the diet affected the amounts of the transcription factor Ybx1 in 23 cell types. They thought this shows that the protein might be related to aging and planned to study it further.
The scientists are now trying to use their findings to discover likely targets for anti-aging drugs and to come up with better ways to enhance longevity.