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The benefits of restricted eating depend on age and gender

Time restricted eating (ART), also known as intermittent fasting diet, consisting of restricting eating to specific times a day, has gained attention in weight loss circles. A new study by scientists at the Salk Institute, in the United States, also shows that it confers multiple health benefits in addition to weight loss, although these benefits may depend on sex and age.

Most studies on ART focus on weight loss in young male mice, but the Salk scientists wanted to determine whether it confers additional benefits to other populations.

Their findings, published in the journal ‘Cell Reports’ show that, although age and gender affect the results, the eating strategy provides multiple benefits for the health of young and old of both sexes, and indicates that it may be an intervention valuable for type 2 diabetes, fatty liver disease and liver cancer, and even infectious diseases such as COVID-19, in humans.

“In many clinical interventions with ART, the main outcome is weight loss, but we have found that it is good not only for metabolic diseases, but also for increasing resistance against infectious diseases and insulin resistance,” explains Satchidananda Panda, professor at the Salk Regulatory Biology Laboratory and holder of the Rita and Richard Atkinson Professorship.

Glucose intolerance is the first step on the slippery slope to nonalcoholic fatty liver disease and liver cancer, one of the few cancers whose incidence and death rates have increased rather than decreased in the past 25 to 30 years.

Breaking the conventional mold of young mice, the researchers fed a diet rich in fat and sugar to male and female mice of two age groups (equivalent to humans aged 20 and 42), restricting feeding to nine hours a day.

The team conducted tests to determine how age and gender affect ART results on a number of health parameters: fatty liver disease; regulation of glucose; muscle mass, performance and endurance; and survival from sepsis, a life-threatening response to infection. They also took the rare step of adapting laboratory conditions to the animals’ circadian clocks (mice sleep during the day and wake up at night), often working with night vision goggles and specialized lighting.

By analyzing the tissues of mice with ART for their chemical composition and processes, the researchers found that regardless of age, sex, or weight loss profile, ART strongly protected against fatty liver disease, a a condition that affects up to 100 million Americans and for which no drug has been approved.

“It was the first time we studied female mice and we weren’t sure what to expect,” says first author Amandine Chaix, a former Panda lab scientist and now an adjunct professor at the University of Utah. females with ART were not protected against weight gain, they continued to show metabolic benefits, including less fatty livers and better controlled blood sugar. “

Glucose tolerance tests administered to mice after 16 hours of fasting indicated that ART was associated with a lower rise in blood glucose and a more rapid return to normal blood sugar levels in both young and male males. in middle-aged females, with a significant improvement in glucose tolerance in young and middle-aged females.

Likewise, middle-aged males and females undergoing ART were able to restore normal blood sugar levels more effectively than control mice, which had food at all times. This finding indicates that ART may be a low- or no-cost way to prevent or treat diabetes, and supports the results of the 2019 laboratory study for metabolic syndrome in humans.

The researchers also found that ART can protect both men and women from sepsis-induced death, a particular danger in ICUs, especially during the pandemic. After giving the mice a toxin that induced a sepsis-like condition, the researchers monitored survival rates for 13 days and found that it protected both male and female mice from dying of sepsis.

ART not only protected against fatty liver disease, diabetes, and death from sepsis, but even allowed male mice to retain and add muscle mass and improve muscle performance (the effect did not occur in females). This finding is especially significant for the elderly, for whom improved muscle performance can help prevent falls.

This surprising discovery points to next steps and new questions for Panda’s lab: Does it increase muscle mass because ART helps muscles repair and regenerate better? What is the impact of ART on muscle metabolism and regeneration? “These are very interesting questions for us, and we are looking forward to studying them in more detail,” acknowledges Panda.

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