Numerous studies have shown the health benefits of temporary food intake, including extending lifespan, making practices such as intermittent fasting a hot topic in the wellness industry. However, it was not yet known exactly how this affects the body on a molecular level and how these changes interact in the various organ systems. Now, scientists are showing in mice how time-limited eating influences 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.

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The results were published in January 2023 in the journal Cell Metabolism have been published have effects on a wide range of health conditions where time-restricted dietary intake has shown potential benefits, including diabetes, heart disease, high blood pressure, and cancer.

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“We found that time-limited eating has a system-wide, molecular effect in mice,” says Professor Satchidananda Panda, lead author and holder of the Rita and Richard Atkinson Chair at the Salk Institute. “Our results open up the opportunity to study in more detail how this nutritional intervention activates genes that are involved in specific diseases, such as cancer.”

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For the study, two groups of mice were fed the same high-calorie diet. One group had free access to food, the other group was only allowed to eat within a time window of nine hours a day. After seven weeks, tissue samples were taken from the brain and 22 groups of organs at various times of the day and night and examined for genetic changes. The samples included tissue from the liver, stomach, lung, heart, adrenal gland, hypothalamus, various parts of the kidney and intestines, and from various areas of the brain.

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The scientists found that 70 percent of mouse genes react to temporary food intake. “By changing the timing of food intake, we were able to change gene expression not only in the intestines or in the liver, but also in thousands of genes in the brain,” says Panda.

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The results provide clues as to how a time-restricted diet can help to cope with illnesses.

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Almost 40 percent of genes in the adrenal gland, hypothalamus and pancreas were influenced by temporary food intake. These organs are important for hormonal regulation. Hormones coordinate functions in various parts of the body and brain, and an imbalance in hormone balance is linked to many diseases, from diabetes to stress disorders. The results provide clues as to how a time-restricted diet can help to cope with these diseases.

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Interestingly, not all sections of the digestive tract were affected equally. While the genes in the two upper sections of the small intestine — the duodenum and the jejunum — were activated by the temporary intake of food, this was not the case in the ileum, the lower end of the small intestine. This finding could usher in a new line of research looking at how shiftwork workplaces that disrupt our 24-hour biological clock (the so-called circadian rhythm) affect digestive diseases and cancers. Previous research by Panda's team has shown that temporary food intake improves the health of firefighters, who usually work shifts.

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The researchers also found that a time-limited diet adjusted the circadian rhythms of several organs in the body. “Circadian rhythms can be found in every cell,” says Panda. “We found that time-limited eating synchronizes circadian rhythms so that they have two main waves: one during fasting and another right after eating. We suspect that this allows the body to coordinate various processes.”

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Next, Panda's team will look more closely at the effects of the time-restricted diet on specific diseases or systems investigated in the study, such as atherosclerosis, a hardening of the arteries, which is often a precursor to heart disease and stroke, and chronic kidney disease.