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An analysis of 1,000 genetically diverse mice on different types of calorie-restricted diets and intermittent fasting shows that the potential benefits of these strategies are more complex than previously thought

 

 

 

  

A longer life may result from consuming fewer calories. Though genetics may have a basic role, the reality may be far more complex than previously believed, despite the repeated emphasis on this theory in recent years. This is clarified by a thorough investigation conducted on nearly a thousand genetically varied mice, which was released on Wednesday in the scholarly journal Nature. While it has been demonstrated that calorie restriction extends life in all rodents, the impact on their well-being varies. The information offers subtleties, specifics, and fresh insights into the intricate connection between food restriction and long life.

 

In a phone interview, biologist Andrea di Francesco and geneticist Gary Churchill, who co-wrote the article with Jackson Laboratory in Maine, noted that calorie restriction "first appeared to extend the lifespan of rodents in the 1930s." Since then, calorie restriction has also been demonstrated to somewhat extend the longevity of numerous other animals, including macaques and worms, making it the proverbial "holy grail of eternal youth." But complexity was hidden beneath the headlines. Churchill says, "It became evident in the early 2010s that not everyone's genetic background benefits equally from this restriction." At that point, he started to plan the study that is now public knowledge.

 

In order to determine the extent to which genetics could affect results, 960 genetically varied female mice were subjected to five distinct treatments. A typical diet was provided to some, a 20% calorie reduction to others, and a 40% reduction to yet others. Mice in two groups were fed an intermittent fasting diet, which involved the mice going without food for one or two days in a row each week. Next, the authors gathered information from over 200 tests measuring blood, metabolic, immunological, functional, and behavioral characteristics. After that, they passed them by.

 

The researchers were shocked to learn that even in the mice on the harshest regime, with their typical diet reduced by 40%, "dietary restriction increased the life expectancy of mice overall." It's a severe limitation. However, except from the fact that the mice were smaller than usual, there was no sign of a problem. Additionally, the researchers discovered that the impact of calorie restriction on life expectancy varied according on age, genetic heritage, the type of food followed, and even the mouse's resilience to its new environment.

 

Millions of people struggle with dieting and not losing weight, yet in the case of mice, it was found to be associated with a higher rise in lifetime. "The animals with higher body fat and glucose levels had longer lifespans. According to Churchill, "I'm assuming that these animals are naturally resilient. The animals that are losing weight are demonstrating to you that they react adversely to diets, and these interventions are unpleasant. In this way, an animal's nutrition only discloses something about its nature.

 

In older rodents, excess fat also appeared to have a protective impact. When their lives are coming to an end, many mammals start to lose weight. It can be an indication of a sickness, but it can also just be the result of aging processes that make them appear to be fading away. This also occurs to people. The scientist continues, "And in mice, a few weeks before they die, they start to lose weight." The capacity to sustain above-average body fat even in old age is a sign of continued good health.

 

It makes sense to us instinctively to believe that a rigorous diet can prolong life, mainly by enhancing cardiovascular health. But the procedure is more intricate. "Reductions in body fat and blood sugar levels were not necessarily correlated with longer life expectancy," the study's researchers concluded. Stated differently, the reason the mice lived longer is not because they were free from issues associated with being overweight. An further element eluded examination. Churchill muses, "There are some good hypotheses about this." For instance, cutting calories alters how a cell functions inside by promoting autophagy and recycling. This phrase, which literally translates as "eating oneself," describes how cells burn off unneeded or defective components to generate energy. Our body would be cellularly cleansed as a result of this. Numerous scientific studies have suggested that autophagy may increase longevity.

 

With our analysis, this is not the case. Churchill clarifies, "We may suspect it, but we did not do studies at the molecular level." When it comes to applying his mouse research findings to a medical setting, the expert is hesitant. The current focus of human studies on calorie restriction and intermittent fasting is on the impact on metabolism. These are significant, he says, but I don't think there will be any evidence in the near future that these diets increase people's life expectancies. In 2021, the journal Science published a meta-analysis of the extant scientific literature, which concluded that, although the abundance of animal research, "it is not possible to determine whether calorie restriction diets affect the biological ageing of people."

The new investigation, in which Marina García Macía, a biologist at the Biomedical Research Institute of Salamanca, Spain, did not participate, is favorable. It's "an in-depth study," in her opinion, with some "novel" conclusions. García Macía finds significance in the large number of rodents used and their gender. In the United States, the National Institutes of Health (NIH) started recommending ten years ago that the sex of mice used in experiments be balanced because, in some sectors (such the study of pain), the percentage of male mice was approximately 80%.

 This study produced a wide range of outcomes, some of which are counterintuitive and occasionally mildly contradicting. In any event, they support earlier scientific research, but they also make clarifications and take some of the oomph out of long-repeated mantras. There might be a direct correlation between dietary limitations and life expectancy. However, there is more nuance to this relationship than first appears.