Numerous studies have shown the health benefits of a time-restricted diet, including an increase in lifespan. But how this exactly affects the body at the molecular level, and how these changes interact across multiple organ systems, is not yet fully understood. Salk scientists have been able to show in studies how time-restricted eating affects gene expression in more than 22 regions of the body and brain. Gene expression is the process by which genes are activated and respond to their environment by making proteins. The findings have implications for a variety of health conditions where time-restricted eating has potential benefits, including diabetes, heart disease, high blood pressure and cancer.

70 Percent of All Genes Respond to Temporary Eating

For the study, two groups of mice were fed the same high-calorie diet. One group received free access to food. The other was restricted to eating within a nine-hour feeding window each day. After seven weeks, tissue samples from 22 organ groups and the brain were taken at different times of the day and night and analyzed for genetic changes. Samples included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, various parts of the kidney and intestines, and various areas of the brain. The authors found that 70 percent of the mice’s genes responded to time-restricted eating. By altering the timing of food intake, they were able to alter gene expression not only in the gut or liver, but also in thousands of genes in the brain.

Almost 40 percent of all genes in the adrenal gland, hypothalamus and pancreas were affected by time-restricted eating. These organs are important for hormone regulation. Hormones coordinate functions in different parts of the body and brain, and hormonal imbalance is implicated in many diseases, from diabetes to stress disorders. The results offer clues as to how a time-restricted diet can help to manage these diseases. Interestingly, not all sections of the digestive tract were equally affected. While genes involved in the upper two sections of the small intestine — the duodenum and jejunum — were activated by time-restricted eating, the ileum, at the bottom of the small intestine, was not. This finding could open a new avenue of research to study how shift work, which disrupts our biological 24-hour clock (called the circadian rhythm), affects digestive diseases and cancer. The researchers also found that time-restricted eating adjusted the circadian rhythms of several organs in the body.

Time-Restricted Eating Against Infectious Diseases And Cancer

Time Restricted Eating is a form of intermittent fasting that involves eating for a limited period of time (eating 8 hours and fasting for the remaining 16 hours). Research by scientists at the Salk Institute shows that in addition to weight loss, time-restricted eating has several health benefits, and these can vary by gender and age. Their findings, published in Cell Reports, show that while age and gender affect outcomes, the dietary strategy offers multiple health benefits for young and old of both sexes, suggesting that this diet may be a valuable intervention in the fight against type 2 -Diabetes, fatty liver disease and liver cancer and even infectious diseases like COVID-19 in humans.

In fact, the experts have found in their investigations that time-restricted food intake is not only good for metabolic diseases, but it also provides increased resistance to infectious diseases and insulin resistance. Glucose intolerance is the first step in developing nonalcoholic fatty liver disease and liver cancer—one of the few cancers whose incidence and death rates have increased rather than decreased over the past 25 to 30 years. In addition, many people are diabetic or prediabetic. These negative trends make finding a simple treatment for glucose intolerance a top priority.

The researchers fed male and female mice of two age groups (equivalent to 20- and 42-year-old humans) a high-fat, high-sugar diet, limiting feeding times to nine hours per day. The team performed tests to determine how age and gender affect TRE results on a variety of health parameters: fatty liver disease, glucose regulation, muscle mass, performance and endurance; and surviving sepsis, a life-threatening response to infection. They also took the rare step of adapting their lab conditions to the animals’ circadian clocks (mice sleep during the day and wake up at night), often using night-vision goggles and special lighting.

Protection Against Diabetes And Sepsis

The researchers analyzed the tissues of mice to determine their chemical composition and processes and found that time restricted eating was highly protective against fatty liver disease regardless of age, gender or weight loss profile. Oral glucose tolerance tests administered to mice after a 16-hour fast showed that this form of fasting was associated with a smaller increase in blood glucose and a faster return to normal blood glucose levels in both young and middle-aged male mice, as well as with a significant improvement in Glucose tolerance in young and older female mice. Similarly, due to time-restricted eating, middle-aged females and males were able to restore normal blood glucose levels more efficiently than control mice, which had food available at all times. This result indicates that this form of fasting can be an inexpensive and simple way to prevent or treat diabetes.

The researchers also found that time restricted eating may protect both men and women from sepsis-induced deaths – a particular hazard in intensive care units, especially during the pandemic. After administering a toxin that induced a sepsis-like condition in the mice, the researchers monitored survival rates for 13 days and found that the time-restricted food intake protected both male and female mice from death from sepsis. It even allowed male mice to preserve muscle mass and improve muscle performance (the effect did not apply to females). This finding is particularly important for older people, for whom improved muscle performance can help to protect against falls.