How Intermittent Fasting Extends Life Spans – Time-Restricted Eating Reshapes 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 displays the interconnected organ systems working smoothly during time-restricted eating, which is represented by the clock in the middle. Credit: Salk Institute

Salk researchers find that timing calorie intake synchronizes circadian rhythms across multiple systems in mice.

Numerous studies have shown health benefits of time-restricted eating including increase in life span in laboratory studies. This has made practices like intermittent fasting a hot topic in the wellness industry. However, exactly how it affects the body on the molecular level, and how those changes interact across multiple organ systems, has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and respond to their environment by creating proteins.

The findings, published in Cell Metabolism on January 3, 2023, have implications for a wide range of health conditions where time-restricted eating has shown potential benefits, including diabetes, heart disease, hypertension, and cancer.

Satchidanananda Panda

Satchidanananda 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 for looking more closely at how this nutritional 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 was given free access to the food. The other group was restricted to eating within a feeding window of nine hours each 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 included tissues from the liver, stomach, lungs, heart, adrenal gland, hypothalamus, different parts of the kidney and intestine, and different areas of the brain.

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

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

Nearly 40 percent of 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 is implicated in many diseases from diabetes to stress disorders. The results offer guidance to how time-restricted eating may help manage these diseases.

Interestingly, not all sections of the digestive tract were affected equally. While genes involved in the upper two portions of the small intestine—the duodenum and jejunum—were activated by time-restricted eating, the ileum, at the lower end of the small intestine, was not. This finding could open a new line of research to study how jobs with shiftwork, which disrupts our 24-hour biological clock (called the circadian rhythm) impact digestive diseases and cancers. Previous research by Panda’s team showed that time-restricted eating improved the health of firefighters, who are typically shift workers.

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 the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect 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 implicated in the study, such as atherosclerosis, which is 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 time-restricted feeding in mammals” by Shaunak Deota, Terry Lin, Amandine Chaix, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, Ling Huang and Satchidananda Panda, 3 January 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 of 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.

8 Comments on "How Intermittent Fasting Extends Life Spans – Time-Restricted Eating Reshapes Gene Expression Throughout the Body"

  1. Well, we know this study was nothing but a propaganda piece since we just had more studies released showing that intermittent fasting does absolutely nothing for anyone.

  2. Massive propaganda spew against IF this week. It is a hit piece.

    Intermittent fasting has become valued from the LowCarb world. Not from the glucose world.

    On LowCarb for weight loss, the body is looking for fat to burn … it has ‘given up’ on expecting carbs to be incoming. So it happily turns to body/visceral stored fat, and you live on that. We call this “The Burn.” Intermittent fasting accelerates The Burn.

    So, the straw man here is this: If you take “IF” out of the above context, use it in mild 16/8 format, but allow the person to “eat whatever” and expect weight loss … as if the time was a magic wand just by itself … that is a setup for failure. You are glucose addicted, and the momentum of burning stored fat does not get going since you are carb-loading during the 8 hours. Moreover, and here is the clincher: eating carbs but putting a 8-hour eating window does nothing but make the person ravenous for food and especially sugar. Self-reporting on the window is dubious. There will be cheating.

    • Excellent response, thanks, John. I’ve healed my fibromyalgia and type-2 diabetes. High fat, medium protein, low carb, intermittent fasting, that’s the ticket! Understand that many things turn to sugar in the body and let them go. You can do it!

  3. Seshu Mahidhara | January 21, 2023 at 4:10 am | Reply

    Intermittent fasting is known for some time. Is it for all ages? I am 85. Can one do it at a late age without going into Problems?

  4. I’ve found intermittent fasting is the only form of dieting that has worked for me after tryind different diets for a dozen years. I’m finally down 30#, i’ve also been able to cut out sugars, and I’m doing better life wise. Do what works for you. I love food and cooking, but eat better now.

  5. Not according to yesterday’s SciTech article, “Not Effective? Popular Anti-Aging Treatments Shown To Have a Limited Impact on Aging”, January 19, 2023. That article defines anti-aging as what results in extended life spans, and it specifically cites fasting as one of the handful of treatments with limited impact on aging.

  6. Am insulin dependent diabetic. How do I do IF without going into hypoglycemia?

  7. I’m surprised this article not anyone in comments mentioned Dr. David Sinclair who has been studying this for over a decade and even has drugs in clinical trials that mimic fasting.

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