Fewer calories, more years, but with nuance: Study explores complex relationship between fasting and longevity | Health and Wellness

Eating fewer calories can lead to longer life. There has been a lot of talk about this idea lately, but it may be much more complex than previously thought, and genetics will play a fundamental role. This is explained by a comprehensive study conducted on almost 1,000 genetically diverse mice, which was published this Wednesday in a scientific journal. Nature. Although calorie restriction has been shown to prolong life in all rodents, the effects on their health have not always been the same. These findings provide nuance, detail, and new insight into the complex relationship between dietary restrictions and longevity.

“Calorie restriction began increasing lifespan in rodents in the 1930s,” explains Gary Churchill, a geneticist at the Jackson Laboratory in Maine and lead author of the study along with biologist Andrea di Francesco, in a telephone conversation. conversation. . Since then, calorie restriction has been shown to prolong the lives of many other creatures, from worms to macaques (albeit modestly), and has become the Holy Grail of eternal youth. But behind the loud headlines, nuances emerged. “In the early 2010s, it became apparent that not all genetic groups benefit equally from this restriction,” Churchill continues. That’s when he began developing the research that is now beginning.

The current work wanted to test the extent to which genetics might influence the results, so they subjected 960 genetically diverse female mice to five different interventions. Some will have a normal diet; others – reducing calorie intake by 20%; and the latter up to 40%. Two groups of mice were put on intermittent fasting, in which the rodents went without food for one or two consecutive days a week. The authors further collected data from approximately 200 assessments of immune, blood, metabolic, functional and behavioral characteristics. And they crossed them.

Thus, they found that “dietary restriction increases the lifespan of mice overall.” Even those who underwent the strictest plan cut 40% of their usual diet, which surprised the researchers. “This is an extreme limitation. “But there was no indication that anything was wrong, except that the mice were smaller than usual.” The researchers also found that the effect of calorie restriction on lifespan varied not only depending on the type of diet consumed, but also depending on the mouse’s age, genetic background, and even how resilient it was to the new situation.

Dieting and not losing weight can be frustrating for millions of people, but in mice it has been shown to be associated with a greater increase in lifespan. “Animals that were able to maintain high levels of fat and glucose in their bodies lived longer. My guess is that these animals have an inherent resilience,” Churchill explains. “These interventions cause stress, and animals that lose weight show 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 occurred in older rodents. Many mammals begin to lose weight towards the end of their lives. Sometimes this is a sign that they have some kind of illness, but sometimes it is a simple process of wear and tear, making it seem as if the elderly person is wasting away. This happens to us humans. “And mice,” the geneticist points out, “several weeks before death begin to lose weight. “The ability to maintain adiposity above normal in older age is an indicator that they are still healthy.”

We tend to intuitively think that a strict diet can increase life expectancy, mainly by improving cardiovascular health. But this is a more complex process. In this study, they confirmed that “reduced body fat and blood sugar levels do not necessarily correlate with increased life expectancy.” That is, the mice lived longer not because they did not have problems associated with excess weight. There was something else that escaped analysis. “There are some good hypotheses about this,” Churchill muses. “For example, calorie restriction changes the internal functioning of the cell by increasing cell recycling and autophagy.” This term, which literally means “eating itself,” serves to explain the process by which cells burn unwanted or damaged components to produce energy. This will serve to cleanse our body at the cellular level. There is a lot of scientific literature suggesting that autophagy can extend lifespan.

This is not the case in this analysis. “We may suspect it, but we haven’t done any research at the molecular level,” Churchill explains. The specialist is cautious when transferring his findings in mice to the medical environment. “Currently, human studies of calorie restriction and intermittent fasting have focused on metabolic effects. These are important things, but I don’t think in the short term we’ll see evidence that these diets extend people’s lifespan,” he laments. A meta-analysis of pre-existing scientific literature published by the journal. Scienceemphasized in 2021 that despite the number of animal studies, “it is impossible to know whether calorie-restricted diets affect biological aging in humans.”

Marina García Macia, a biologist at the Salamanca Institute of Biomedical Research, is positive about the analysis, which she did not work on. He believes it is a “large, longitudinal study” with some “new” findings. He appreciates the large number of rodents used and the fact that they are female. Ten years ago, the US National Institutes of Health (NIH) began recommending gender parity for mice used in experiments, as in some areas (such as pain studies) the rate was around 80%.

The results of this study are numerous, sometimes slightly contradictory, and sometimes counterintuitive. In any case, they are consistent with previous scientific literature, but limit and detract from the enthusiasm of some of the mantras repeated over the years. Dietary restrictions may have a clear link to life expectancy. But this relationship is more complex than previously thought. Blanco agrees with this idea and reflects on how science is valued in the academic and journalistic world. “I think it’s wiser not to draw very clear conclusions,” he says. “We are accustomed to the fact that everything that is published is exclusively positive. It seems like we are all going to cure disease X with our ideas. But the reality is not like that. There are positive data and negative data in research, it is better to teach and reason about everything.”