How Intermittent Fasting Extends Longevity – Time-restricted eating alters gene expression throughout the body

Time-restricted eating reshapes gene expression

Time-restricted eating reshapes gene expression throughout the body. In this illustration, the Ferris wheel shows that the interconnected organ systems operate smoothly during time-restricted eating, which is represented by the clock in the center. Credit: Salk Institute

Salk researchers discover that the timing of caloric intake synchronizes circadian rhythms across multiple systems in mice.

Numerous studies have shown health benefits of time-restricted eating, including increased longevity in lab studies. This has made practices like intermittent fasting a hot topic in the wellness industry. However, exactly how the body is affected on a molecular level and how those changes interact across multiple organ systems is not well understood. Now, in mice, Salk scientists are showing how time-restricted eating affects gene expression in more than 22 parts 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, published in Cell Metabolism on Jan. 3, 2023, has implications for a wide variety of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

Satchidananda Panda

Satchidananda Panda. Credit: Salk Institute

“We found that there is a system-wide, molecular impact of time-restricted eating in mice,” says Professor Satchidananda Panda, senior author and holder of the Rita and Richard Atkinson Chair at Salk. “Our results open the door to a closer look at how this dietary intervention activates genes involved in specific diseases, such as cancer.”

For the study, two groups of mice were fed the same high-calorie diet. One group received free access to the food. The other group was restricted to eating within a nine-hour feeding window per day. After seven weeks, tissue samples were collected from 22 organ groups and the brain at different times of the day or night and analyzed for genetic changes. Samples include tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, various parts of the kidney and intestine, and various parts of the brain.

The authors found that 70 percent of the mouse genes respond to time-restricted eating.

“By changing the timing of food, we were able to change gene expression not only in the gut or in the liver, but also in thousands of genes in the brain,” says Panda.

Nearly 40 percent of the genes in the adrenal gland, hypothalamus and pancreas were affected by time-restricted eating. These organs are important for hormonal regulation. Hormones coordinate functions in different parts of the body and brain, and hormonal imbalance has been implicated in many diseases, from diabetes to stress disorders. The results provide some guidance on how time-restricted eating may help manage these diseases.

Interestingly, not all parts of the digestive tract were equally affected. While genes involved in the top two parts 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 line of research to study how shift work, which disrupts our 24-hour biological clock (called the circadian rhythm), affects digestive diseases and cancer. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who typically work shifts.

The researchers also found that time-restricted eating aligned the circadian rhythms of multiple organs of the body.

“Circadian rhythms are everywhere in every cell,” says Panda. “We found that time-restricted eating synchronized circadian rhythms to have two major waves: one during fasting and another right after eating. We suspect that this allows the body to coordinate different processes.”

Next, Panda’s team will take a closer look at the effects of time-restricted eating on specific conditions or systems involved in the study, such as atherosclerosis, a hardening of the arteries that is often a precursor to heart disease and stroke. as well as chronic kidney disease.

Reference: “Diurnal transcriptome landscape of a multi-tissue response to temporal feeding in mammals” By Shaunak Deota, Terry Lin, Amandine Chaix, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, Ling Huang, and Satchidananda Panda, January 3, 2023, Cell Metabolism.
DOI: 10.1016/j.cmet.2022.12.006

Other authors include Shaunak Deota, Terry Lin, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, and Ling Huang van Salk; and Amandine Chaix of the University of Utah.

The research was supported by the National Institutes of Health (grants CA258221, DK115214, CA014195, and AG065993) and the Wu Tsai Human Performance Alliance.

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