How can you feel better, prevent chronic disease and live longer? The answer may lie in what you eat!Recent research published in Cell by American and Chinese scientists provides great detail on the cellular impact of a lower-calorie diet in rats. Although the benefits of calorie restriction have been known for a while, new research shows the nitty gritty of cellular pathways and how eating less protects against aging.Juan Carlos Izpisua Belmonte, one of the first authors of the research and a professor in Salk’s Gene Expression Lab notes that the team's research can show all the changes that happen on a single-cell level. He believes this data provides scientists with targets to be able to develop drugs that impact human aging.While aging is inevitable, it is unfortunately the biggest risk factor for chronic diseases including cancer, diabetes, dementia, and metabolic syndrome. In animal models, calorie restriction has been shown to be an effective intervention against several age-related diseases. Until now, it was unknown how calorie restriction influenced individual cells and how the organism changed as it aged.Belmonte and his colleagues (who include three alumni from his Salk lab and run their own research in China) evaluated rats that ate 30% less calories, comparing them to rats on normal calorie diets. From the age of 18 months to 27 months, the animals’ diets were controlled. This would be like a person being on a calorie-restricted diet from the age of 50 to 70.Belmonte’s team isolated and evaluated over 168,700 cells from 40 cell types in 56 rats from the start and end of the diet. The cells were from fat, liver, kidney, aorta, skin, bone marrow, brain, and muscle tissue. Single-cell genetic sequencing technology was used in each isolated cell to gauge the genes’ activity levels. The researchers then compared young and old mice on the diets.Several changes that happened to the rats on the normal diet as they grew older did not occur in the rats on the restricted diet. Even as the rats on restricted diets got older, their tissues and cells resembled those of young rats. Of the age-related changes in cell composition seen in the normal diet rats, 57% were not seen in the rats on the calorie restricted diet.Co-author Guang-Hui Liu, a professor at the Chinese Academy of Sciences, believes that their research provided information on the effect of calorie restriction on cell types as well as what occurs at a single-cell level during aging. The cells and genes most impacted by the diet related to immunity, inflammation, and lipid metabolism. As the control rats aged, the number of immune cells in almost all tissues studied increased, but were not affected by age in calorie-restricted rats. In brown fat tissue, the expression levels of many anti-inflammatory genes were reversed to those seen in young animals.The researchers note that the biggest find in the current study is that the rise in the inflammatory response that occurs during aging could be repressed through calorie restriction. When the scientists honed in on transcription factors, the master switches that can alter gene activity and were affected by caloric restriction, one stood out. Transcription factor Ybx1 were changed in 23 different cell types by the diet. Researchers think Ybx1 may be an age-related transcription factor and are looking into more research on its effects.Concepcion Rodriguez Esteban, one of the paper’s authors, notes, “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 information is now being used by the team to investigate aging drug targets and utilize strategies towards increasing health and life span.Now that we've covered the science, here's some advice to give your clients about reducing calories to reduce the ills of aging:

• Include more nutrient-dense, plant-based foods in your diet, such as leafy greens, berries, citrus fruit, beans, and whole grains.
• Limit intake of high-fat, high-calorie desserts, high-sugar beverages, fried foods and other calorie-dense foods.
• Reduce serving sizes at meals to lower calorie intake. Use smaller plates.
• Pay attention to how often you eat and what you snack on. Are you truly hungry, or is something eating you that’s making you eat?
• Eat your largest meal earlier in the day and gradually taper servings down through the day.
• Balance calories with physical activity. Stay active!
• Limit or avoid alcohol. It provides empty calories and is considered a toxin to your body.

By Lisa Andrews, MEd, RD, LDPDF Handout:References:

1. https://www.cdc.gov/nchs/fastats/heart-disease.htm
2. Shuai Ma, Shuhui Sun, Lingling Geng, Moshi Song, Wei Wang, Yanxia Ye, Qianzhao Ji, Zhiran Zou, Si Wang, Xiaojuan He, Wei Li, Concepcion Rodriguez Esteban, Xiao Long, Guoji Guo, Piu Chan, Qi Zhou, Juan Carlos Izpisua Belmonte, Weiqi Zhang, Jing Qu, Guang-Hui Liu. Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging. Cell, 2020; DOI: 10.1016/j.cell.2020.02.008