Hunger Extends Life in Flies Independently of Calorie Intake
Calorie restriction is the practice of eating fewer calories while still obtaining an optimal intake of micronutrients. In recent years work in flies has expanded the understanding of how perception of food and regulation of hunger interacts with the health benefits and slowed aging that result from calorie restriction. Allowing flies to scent food removes the benefits of a lowered calorie intake, for example.
Here, researchers generate a lineage of flies that can be induced to be constantly hungry, and they find that this produces similar benefits to calorie restriction even while the flies eat more than their unmodified peers. Relatedly, work on various different forms of calorie restriction in mammals suggests that time spent hungry is the common denominator leading to slowed aging and improved health; the signaling related to hunger is an important determinant of altered cell behavior, perhaps, not just the present availability of nutrients to any given cell.
Researchers induced hunger in flies in several ways. The first was to alter the amount of branched-chain amino acids, or BCAAs, in a test snack food and later allow the flies to freely feed on a buffet of yeast or sugar food. Flies fed the low-BCAA snack consumed more yeast than sugar in the buffet than did the flies fed the high-BCAA snack. This kind of preference for yeast over sugar is one indicator of need-based hunger. The researchers note that this behavior wasn't due to the calorie content of the low-BCAA snack; in fact, these flies consumed more food and more total calories. When flies ate a low-BCAA diet for life, they also lived significantly longer than flies fed high-BCAA diets.
To look at hunger apart from dietary composition, researchers used a unique technique, activating neurons associated with the hunger drive in flies using exposure to red light, using a technique called optogenetics. These flies consumed twice as much food than did flies who were not exposed to the light stimulus. The red-light activated flies also lived significantly longer than flies used as a control. What's more, the team was able to map the molecular mechanics of hunger to changes in the epigenome of the neurons involved - and to identify that neurons responded to the presence or absence of a specific BCAA, isoleucine, in the diet. These changes can affect how much of specific genes are expressed in the brains of flies and, consequently, their feeding behavior and aging.
Link: https://www.michiganmedicine.org/health-lab/feeling-hunger-itself-may-slow-aging-flies