From low-carb to intermittent fasting, from surgery to Ozempic—people turn to a seemingly endless variety of diets, procedures, and medications to lose weight. While it has long been understood that limiting the amount of food consumed can promote healthy aging in a wide range of animals, including humans, a new study from the University of Michigan has revealed that the feeling of hunger itself can be enough to delay aging.
Previous research has shown that even the taste and smell of food can reverse the beneficial and life-extending effects of dietary restriction, even without its consumption.
These intriguing findings led first author Kristy Weaver, Ph.D., principal investigator Scott Pletcher, Ph.D., and their colleagues to examine whether changes in the brain that trigger the urge to forage might be behind a longer life.
“We have divorced [the life extending effects of diet restriction] of all the nutritional manipulations of the diet that researchers have worked on for many years to say are not necessary,” Pletcher said. “The perception that there is not enough food is enough.”
To do this, they induced hunger in the flies in various ways. The first was to alter the amount of branched-chain amino acids, or BCAAs, in a test snack and then allow the flies to feed freely on a buffet of yeast or sugar. Flies fed the low BCAA snack consumed more yeast than sugar at the buffet than did flies fed the high BCAA snack. This kind of preference for yeast over sugar is an indicator of need-based hunger.
The researchers noted that this behavior was not due to the calorie content of the low-BCAA snack; in fact, these flies consumed more food and more total calories. When the flies ate a low-BCAA diet for life, they also lived significantly longer than flies fed high-BCAA diets.
To look at hunger in addition to diet composition, they used a unique technique, activating neurons associated with the hunger drive in flies by exposure to red light, using a technique called optogenetics. These flies consumed twice as much food as the flies that were not exposed to the light stimulus. The red light activated flies also lived significantly longer than the control flies.
“We think we have created a type of insatiable hunger in the flies,” Weaver said. “And by doing so, the flies lived longer.”
Furthermore, the team was able to map the molecular mechanics of starvation to changes in the epigenome of the neurons involved, and identify which neurons responded to the presence or absence of a specific amino acid in the diet. These changes may affect the number of specific genes that are expressed in the brain of the flies and consequently their feeding and aging behaviour.
The authors note that caution should be exercised before applying the findings to people, but “there are many reasons to hope that the discovered mechanisms are likely to modulate hunger drives in other species.”
Next, they plan to examine how the impulse to eat for pleasure, present in both flies and people, may also be related to lifespan.
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