Sensory and Neuronal Influences on Fly Longevity

Life spans in short-lived animals can be made to vary far more in response to circumstances than the life spans of longer-lived animals. In the case of calorie restriction there is an evolutionary explanation in that if periods of famine are longer in relation to length of life there is a selection pressure for the response to scarcity to induce greater longevity in individuals. There will probably be similar explanations for the many other ways in which a given approach can extend life in mice or flies or worms far more than it can in longer-lived mammals.

One of the discoveries made in studies of fly longevity is that neural sensing plays a strong role in guiding life span variations. Flies in fact have all sorts of interesting peculiarities in their linkage between metabolism and aging, such as the great importance of intestinal function to longevity, and the sensory influences discussed below, but it remains to be seen how many of these are of any real relevance to mammals.

The goal of Dr. Pletcher's lab is to identify and investigate genetic mechanisms that are important in aging and age-related diseases in humans by focusing on equivalent, conserved processes in the fruit fly model, Drosophila melanogaster. He views aging as a "physiological behavior" and is seeking to understand the neural mechanisms of its coordination and execution. In a recent seminar at the Buck Institute, Dr. Pletcher discussed how substances like water and sugar can initiate changes in aging processes by specifically affecting sensory neurons. His lab found that in flies, bitter tastes have negative effects on lifespan while sweet tastes had positive effects. Interestingly, the ability to taste water had the most significant impact: flies that couldn't taste water lived up to 40% longer. One possible explanation for these results is that flies that can't taste water might compensate for this perceived water shortage by converting large amounts of their own body fat into water.

"We are interested in learning how social interactions and sensory perception affect lifespan and healthspan. We are currently collaborating with a few mouse labs to answer these questions. Some of the studies we are conducting involve putting mice on a restricted diet while housing them near other mice that get to eat food. We then ask whether deprivation in this type of environment affects glucose intolerance or other physiological characteristics in the dietary restricted mice. Ultimately, we want to understand how environmental perception affects lifespan. We want to determine what's happened in cells that cause lifespan changes at the molecular level. However, we are also interested in determining whether there's a specific region of brain where lifespan is consistently manipulated when you stimulate those neurons - in another word, a longevity regulatory center."



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