Let’s Take a Closer Look at Neurons and Lifespan in Fruit Flies!

Published on July 5, 2022

Imagine you’re in charge of a department store, and reducing insulin signaling in different departments affects employee performance and their ability to age gracefully. Recent research in fruit flies (Drosophila melanogaster) has shown that when insulin/IGF-like signaling is reduced specifically in serotonergic neurons, it extends the lifespan of female flies without impacting their ability to move around. However, reducing insulin signaling in other neuronal subtypes, such as cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons, either had no effect or had a negative impact on lifespan and locomotor abilities. These findings suggest that different types of neurons respond differently to changes in insulin signaling when it comes to regulating lifespan and movement. This research sheds light on the intricate relationship between insulin signaling and specific neuronal subtypes, paving the way for further investigations into the mechanisms underlying aging and behavior in animals.

Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.

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