BEIJING, March 2 (Xinhua) — What should you do if you want to reduce inflammation throughout the body, delay the ongoing and prolong the life of age-related diseases? The answer is: eat less. That’s the conclusion of a new study by scientists from China and the United States that provides the most detailed report yet on the effects of calorie-restricted diets on rat cells. Although the benefits of limiting calorie intake have long been known, the results of this new study suggest that such restrictions can prevent aging of cellular pathways, as detailed in the February 27, 2020 issue of the journal Cell.
The figure shows the effects of heat restriction on all aspects of cell function, with the overall result of reducing inflammation and reducing the activity of many aging-related genes
“We already know that limiting calorie intake can extend life,” said Juan Carlos Izpisua Belmonte, co-author of the paper and a professor at the Gene Expression Laboratory at the Salk Institute in the United States. But now we show all the changes that lead to longer life at the single-cell level. This gives us a goal of eventually treating human aging with drugs. “
Aging is the highest risk factor for many human diseases, including cancer, dementia, diabetes and metabolic syndrome. In animal models, heat restriction has been shown to be one of the most effective interventions against these age-related diseases. Although researchers know that as organisms age, individual cells change many, they don’t know how heat restriction affects these changes.
In the new paper, researchers at the Salk Institute, the Institute of Zoology of the Chinese Academy of Sciences, the Institute of Biophysics of the Chinese Academy of Sciences and others compared the difference between rats that consumed 30 percent less calories and mice with a normal diet. The rats had between 18 and 27 months of age, roughly equivalent to those aged 50 to 70 who followed a calorie-restricted diet.
At the beginning and end of the diet, the team isolated and analyzed a total of 168,703 cells from 40 cell types in 56 rats. These cells come from adipose tissue, liver, kidneys, aorta, skin, bone marrow, brain and muscles. In each isolated cell, the researchers used single-cell gene sequencing techniques to measure the activity level of the gene. They also studied the overall composition of cell types in any given tissue. They then compared the differences between older and young mice in each diet.
As normal-eating rats aged, many of the changes in their bodies did not occur in diet-limited rats; even in old age, many of the tissues and cells of dietary mice were very similar to those of young rats. Overall, 57 percent of age-related cell composition changes in normal-eating rat tissue did not occur in rats with a calorie-restricted diet. Ma Shuai, one of the study’s first authors and a researcher at the Institute of Zoology of the Chinese Academy of Sciences, said that not only did the rats slim muse visible to the naked eye, but various signs showed that they were younger than rats of the same age.
“This approach not only tells us about the effects of heat restriction on these cell types, but also provides the most complete and detailed study of what happens at the single-cell level during aging,” said Liu Guanghui, a co-author of the study and a researcher at the Institute of Zoology of the Chinese Academy of Sciences. “
Some of the cells and genes most affected by diet are associated with immunity, inflammation and lipid metabolism. In almost every tissue studied, the number of immune cells increased significantly with the aging of the control group of rats, but in rats with limited calorie intake, the number of immune cells was not affected by age. In brown adipose tissue, a calorie-restricted diet restores the expression level of many anti-inflammatory genes to the level of young rats.
“The main finding of this study is that heat restriction can systematically inhibit the increase in inflammatory responses during aging,” said Qu Jing, a co-author of the study and a researcher at the Institute of Zoology of the Chinese Academy of Sciences. “The inflammation here is a stress response of the immune system to damage and infection, which usually helps repair the damage and protects the body.
Transcription factors are essentially the main switch that can make extensive changes to many other genetic activity, and when researchers analyzed transcription factors that might be altered by heat restriction, they found that one of them was particularly noticeable. In 23 different types of cells, the level of the transcription factor Ybx1 was altered by diet. The researchers believe Ybx1 may be an aging-related transcription factor and plan to do more research on its effects.
“People say, ‘What’s what you eat is what’, and we find that in many ways,’ said Concepcion Rodriguez Esteban of the Salk Institute, another author of the paper. The state of the cells obviously depends on how you interact with the environment, including what you eat and how much you eat. After comparing the molecular network stakes of two groups of rats, the researchers came to the key conclusion that limiting calorie intake — keeping “seven full” — could effectively reverse changes in the immune system caused by aging.
This is the first time that scientists have systematically analyzed the cellular and molecular changes of the body at the multi-organ and multi-tissue levels, not only revealing that chronic inflammation is a common feature of aging in mammalian organisms and organs, but also suggesting that proper dieting can delay aging and even reverse a series of physiological indicators associated with aging.
Now, the research team is trying to use this information to find targets for the effects of aging drugs, and to develop strategies to extend life expectancy and health. “We also provide new biological markers for early warning of aging, linked to humans, and perhaps we can look for these key factors affecting aging in human blood, to explore whether humans meet this law, and then use these factors as an assessment indicator to explore the effects of behavior such as exercise and drinking on aging,” Qu said. (Any day)