A new study reveals that the health benefits associated with intermittent fasting and calorie restriction are not so much related to the fasting itself as to what happens in the body afterward during the refeeding phase.
It turns out that the body's complex readjustment of its metabolic processes may be the real key to longevity.
The research team from UT Southwestern Medical Center found that the positive effect of fasting on lifespan is not directly caused by abstaining from food, but by the biological changes that occur when food is resumed.
The researchers based their findings on experiments conducted on Caenorhabditis elegans, a simple organism widely used in scientific research, with the potential for these results to have future implications for understanding human health and aging.
During fasting, cells rapidly begin to consume their glucose stores, then switch to burning stored fat for energy. This process is controlled by proteins, most importantly a protein known as NHR-49, which is activated when energy levels drop, stimulating cells to use fat as an alternative energy source.
But when refeeding occurs, the picture changes completely; the activity of this protein stops, the process of breaking down fats decreases, and the cells begin to rebuild their natural energy reserves.
Researchers say that scientific focus has not previously been sufficiently directed toward this transitional phase between fasting and eating, even though it may be the most important in determining health benefits.
In a previous study, the same team discovered that the NHR-49 protein not only regulates fat burning, but also acts as a sensor for fat stores within cells, making it a pivotal element in energy balance.
To understand its role in extending lifespan, researchers genetically modified C. elegans worms to remove this protein, then subjected them to a 24-hour fast. The results were surprising: the longevity-extending effect of fasting was not diminished but persisted, with the worms' average lifespan increasing by approximately 41%, and they exhibiting greater activity and vitality even in old age.
The researchers then moved to the refeeding phase to understand what happens when the protein's activity is disrupted. They discovered that it is deactivated by an enzyme known as CK1α1, which chemically modifies the NHR-49 protein through a process called phosphorylation, thus rendering it inactive.
But when the researchers tried to keep this protein active even after refeeding, the longevity-extending benefits disappeared completely, despite the fasting continuing initially.
These results suggest that the ability to "switch off" the activity of fat-burning proteins after fasting may be a key element in achieving health benefits and longevity.
Researchers believe that understanding this mechanism could open the door to developing treatments or nutritional interventions that mimic the effects of fasting, without the need for prolonged abstinence from food, which could help in the future to improve health and slow aging in humans.
The study was published in the journal Nature Communications.
