How caloric restriction prevents negative effects of aging in cells
If you would like to scale back levels of inflammation throughout your body, delay the onset of age-related diseases, and live longer, eat less food. that is the conclusion of a replacement study by scientists from the US and China that gives the foremost detailed report back to date of the cellular effects of a calorie-restricted diet in rats. While the advantages of caloric restriction have long been known, the new results show how this restriction can protect against aging in cellular pathways, as detailed in Cell on February 27, 2020.
“We already knew that calorie restriction increases lifetime , but now we’ve shown all the changes that occur at a single-cell level to cause that,” says Juan Carlos Izpisua Belmonte, a senior author of the new paper, professor in Salk’s organic phenomenon Laboratory and holder of the Roger Guillemin Chair. “This gives us targets that we may eventually be ready to act on with drugs to treat aging in humans.”
Aging is that the highest risk factor for several human diseases, including cancer, dementia, diabetes and metabolic syndrome. Caloric restriction has been shown in animal models to be one among the foremost effective interventions against these age-related diseases. And although researchers know that individual cells undergo many changes as an organism ages, they need not known how caloric restriction might influence these changes.
In the new paper, Belmonte and his collaborators – including three alumni of his Salk lab who are now professors running their own research programs in China – compared rats who ate 30 percent fewer calories with rats on normal diets. The animals’ diets were controlled from age 18 months through 27 months. (In humans, this is able to be roughly like someone following a calorie-restricted diet from age 50 through 70.)
At both the beginning and therefore the conclusion of the diet, Belmonte’s team isolated and analyzed a complete of 168,703 cells from 40 cell types within the 56 rats. The cells came 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 live the activity levels of genes. They also checked out the general composition of cell types within any given tissue. Then, they compared old and young mice on each diet.
Many of the changes that occurred as rats on the traditional diet grew older didn’t occur in rats on a restricted diet; even in adulthood , many of the tissues and cells of animals on the diet closely resembled those of young rats. Overall, 57 percent of the age-related changes in cell composition seen within the tissues of rats on a traditional diet weren’t present within the 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 foremost complete and detailed study of what happens at a single-cell level during aging,” says co-corresponding author Guang-Hui Liu, a professor at the Chinese Academy of Sciences.
Some of the cells and genes most suffering from the diet associated with immunity, inflammation and lipid metabolism. the amount of immune cells in nearly every tissue studied dramatically increased as control rats aged but wasn’t suffering from age in rats with restricted calories. In brown fat – one sort of fat tissue – a calorie-restricted diet reverted the expression levels of the many anti-inflammatory genes to those seen in young animals.
“The primary discovery within the current study is that the rise within the inflammatory response during aging might be systematically repressed by caloric restriction” says co-corresponding author Jing Qu, also a professor at the Chinese Academy of Sciences.
When the researchers homed in on transcription factors – essentially master switches which will broadly alter the activity of the many other genes – that were altered by caloric restriction, one stood out. Levels of the transcription factor Ybx1 were altered by the diet in 23 different cell types. The scientists believe Ybx1 could also be an age-related transcription factor and are planning more research into its effects.
“People say that ‘you are what you eat,’ and we’re finding that to be true in many ways,” says Concepcion Rodriguez Esteban, another of the paper’s authors and a staff researcher at Salk. “The state of your cells as you age clearly depends on your interactions together with your environment, which incorporates what and the way much you eat.”
The team is now trying to utilize this information in an attempt to get aging drug targets and implement strategies towards increasing life and health span.
Other researchers on the study were Shuai Ma, Shuhui Sun, Lingling Geng, Moshi Song, Wei Wang, Yanxia Ye, Qianzhao Ji, Zhiran Zou, Si Wang and Qi Zhou of the Chinese Academy of Sciences; Xiaojuan He, Wei Li, Piu Chan and Weiqi Zhang of Xuanwu Hospital Capital Medical University; Xiao Long of Peking Union Medical College Hospital; and Guoji Guo of Zhejiang University School of drugs .
The work and researchers involved were supported by grants from the National Key Research and Development Program of China, the Strategic Priority Research Program of the Chinese Academy of Sciences, the National science Foundation of China, Beijing science Foundation, Beijing Municipal Commission of Health and birth control , Advanced Innovation Center for Human Brain Protection, the State Key Laboratory of Membrane Biology, the Moxie Foundation, and therefore the Glenn Foundation