Eating fewer calories can lead to living longer. The idea has been repeated insistently in recent times, but it could be much more complex than previously believed and genetics would have a fundamental role. This is explained by a complete study carried out on almost 1,000 genetically diverse mice that is published this Wednesday in the scientific journal Nature. Although calorie restriction was shown to extend life in all rodents, the effects on their health were not always the same. The data provide nuances, details and new insights into the complex relationship between dietary restriction and longevity.
“Calorie restriction began to be shown to extend the lifespan of rodents in the 1930s,” explains Gary Churchill, a geneticist at the Jackson Laboratory (Maine, United States) and lead author of the study along with biologist Andrea di Francesco, in a telephone conversation. . Since then, calorie restriction has also been shown to prolong the existence of many other beings, from worms to macaques (albeit modestly), and has become the Holy Grail of eternal youth. But behind the big headlines, nuances appeared. “In the early 2010s, it began to be seen that not all genetic backgrounds benefit equally from this restriction,” Churchill continues. It was then that he began to devise the study that is now being launched.
The current work wanted to test to what extent genetics could affect the results, so they subjected 960 genetically diverse female mice to five different interventions. Some would have a normal diet; others, a reduction in caloric intake of 20%; and the latter, up to 40%. There were two groups of mice that were put on an intermittent fasting diet, in which the rodents went without eating one or two consecutive days per week. Next, the authors collected data from about 200 assessments of immune, blood, metabolic, functional and behavioral traits. And they crossed them.
They thus discovered that “dietary restriction increased the life expectancy of mice in general.” Even in those who underwent the strictest plan of reducing 40% of their normal diet, which surprised the researchers. “It is an extreme restriction. “But there was no indicator that anything was wrong, other than the mice were smaller than normal.” The researchers also found that the effects of calorie restriction on life expectancy were different not only depending on the type of diet followed, but also depending on the age, genetic ancestry and even the resistance of the mouse to its new situation.
Going on a diet and not losing weight can be frustrating for millions of humans, but in the case of mice, this fact was shown to be related to a greater increase in life expectancy. “Animals that were able to keep their body fat and glucose levels high lived longer. And my assumption here is that these animals have an intrinsic resilience,” explains Churchill. “These interventions are stressful and animals that are losing weight are showing you that they respond negatively to the diet. In this sense, diets simply reveal something about the nature of the animal,” he adds.
Another case in which more fat seemed to have a protective effect was in elderly rodents. Many mammals, near the end of their life, begin to lose weight. Sometimes it is a sign that they have some illness, but other times it is a simple process of wear and tear, it gives the impression that the elderly person is wasting away. This happens to us humans. “And for mice,” the geneticist points out, “a few weeks before they die they begin to lose weight. “The ability to maintain adiposity beyond normal, at an advanced age, is an indicator that they are still healthy.”
We tend to think, intuitively, that a strict diet can increase life expectancy, mainly by improving cardiovascular health. But it is a more complex process. In this study they confirmed how “the reduction in body fat and blood sugar levels were not necessarily correlated with a longer life expectancy.” That is to say, it is not that the mice lived longer because they did not have problems related to being overweight. There was something else that escaped analysis. “There are some good hypotheses about this,” Churchill reflects. “For example, calorie limitation changes the internal functioning of a cell, increasing cell recycling and autophagy.” This term, which literally means “eating oneself,” serves to explain the process by which cells burn their unnecessary or damaged components to produce energy. This would serve to cleanse our body at a cellular level. There is much scientific literature suggesting that autophagy could extend lifespan.
This is not the case of this analysis. “We may suspect it, but we did not do studies at the molecular level,” explains Churchill. The specialist is cautious when transferring his results with mice to the medical environment. “At the moment, the studies that have been carried out in humans on calorie restriction and intermittent fasting focus on the metabolic effects. These are important things, but I don’t think that in the short term we will see evidence that these diets extend people’s life expectancy,” he laments. A meta-analysis of the pre-existing scientific literature, published by the journal Sciencehighlighted in 2021 how, despite the number of animal studies, “it is not possible to know if calorie restriction diets affect the biological aging of people.”
Marina García Macía, biologist at the Salamanca Biomedical Research Institute, positively values this analysis, on which she has not worked. He considers that it is “a great, long study” and with some “new” conclusions. He positively values the large number of rodents used and the fact that they are female. The National Institutes of Health (NIH) of the United States began to recommend a decade ago that there be parity in the sex of the mice used in experiments, since these tended to be males in percentages that in some fields (such as the study of pain) were around 80%.
The results of the present study are many, sometimes slightly contradictory and sometimes counterintuitive. In any case, they agree with previous scientific literature, but they qualify and diminish the enthusiasm of some mantras that have been repeated for years. Dietary restrictions may have a clear relationship with life expectancy. But this relationship is more complex than previously thought. Blanco agrees with this idea and reflects on the way science is valued in the academic and journalistic world. “I think that not having very clear conclusions is wiser,” he points out. “We are used to everything that has to be published being excessively positive. It seems as if we were all going to cure X disease with our ideas. And reality is not like that. In research there are positive data and negative data, it is better to teach everything and reason about it.”