DETROIT — A Wayne State University researcher is using a tiny worm to better understand how human physiology and behavior are affected by the environment.

In studying the worm C. elegans, Joy Alcedo, Ph.D., assistant professor of biological sciences in the College of Liberal Arts and Sciences, recently found that the animals' sensory neurons affect lifespan through recognition of food types, which include different bacteria.

Her team also found that those neurons act with a neuropeptide receptor similar to one existing in humans. Neuropeptides are small proteins released from neurons that regulate important biological processes by activating receptor proteins and their signaling cascades. Expressed in both the sensory system and the reproductive system, they found that this particular neuropeptide receptor influences the C. elegans' lifespan in a manner dependent on the outer structure of the worm's live E. coli food source.

"Environmental cues, like the type of food source, level of food intake or various forms of stress, have been shown to influence lifespan," Alcedo said. "These different cues presumably modulate the activities of different signaling pathways that have previously been shown to affect longevity."

Alcedo's study, "Elucidation of the Mechanisms through Which the Neuropeptide Receptor NMUR-1 Mediates the Sensory Influence on C. elegans Physiology and Lifespan," has been supported by the Novartis Research Foundation and a grant from the Swiss National Science Foundation, based on results that the team published in the journal PLoS Biology in 2010.

Although Alcedo's data suggest that NMUR-1 is required to process specific food-derived information in influencing lifespan, the precise mechanisms involved remain unclear. Thus, she aims to understand the mechanisms through which the receptor mediates the sensory influence on lifespan and alters C. elegans' physiology in a food source-dependent manner.

Discovering a role for NMUR-1 in affecting C. elegans' lifespan through the type of diet provides a genetic framework for clarifying how specific food cues, as well as the sensory system, influence lifespan.

"Since this receptor is also found in humans, understanding how it affects C. elegans' lifespan may lead us to understand how a similar pathway could function within us," Alcedo said. "This could suggest that the large repertoire of neuropeptides and their receptors in C. elegans and other animals serve to process distinct environmental information into physiological responses that would optimize survival."

Alcedo believes her studies may also yield much-needed insight into how different types of diet contribute to age-related diseases like obesity and diabetes; such diseases presumably involve the deregulation of specific activities of different neuropeptide signaling pathways.

In a related study, "Two Insulin-like Peptides Antagonistically Regulate Aversive Olfactory Learning in C. elegans," published in the journal Neuron in February, Alcedo's team, in collaboration with the team of Yun Zhang at Harvard University, found that specific insulin-like peptides regulate distinct processes, such as learning versus development, in different ways. For example, they can act opposite from each other in certain cases or synergistically in others.

Previous work from her team also showed that C. elegans' insulin-like peptides can encode sensory information to regulate various developmental processes, raising the possible existence of a combinatorial insulin-like peptide code for physiology. The study in Neuron suggests that such a code might not be limited to developmental processes, but can also be extended to other processes, such as learning. Her team's study of the insulin-like peptides has been funded by the Novartis Research Foundation.

"Because of the high degree of similarities between C. elegans and humans, studies of the 40 C. elegans' insulin-like peptides can provide insights into the activities of the ten-member human insulin-like peptide family, which includes insulin," Alcedo said. "These studies raise the possibility that a similar combinatorial insulin-like peptide code, which might be analog in nature, can regulate different human physiological and behavioral processes.

"Thus, such a possibility can help develop therapeutic strategies against many human insulin-like peptide-associated diseases such as the metabolic syndrome, different types of cancer and neurological disorders."

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