Tinkering with Sensory Pathways as an Approach to the Development of Calorie Restriction Mimetics

Most laboratory species - such as flies, worms, mice, and other mammals - have been shown to age somewhat more slowly in response to calorie restriction; it changes near every measure of metabolism and improves near every measure of health. The effects on lifespan are much more pronounced in short-lived species than in long-lived species such as our own, but the effects on human health are still pretty impressive. It has been a few years now since researchers first found that the calorie restriction response has some dependency on sensory perception of food in species such as nematode worms and flies. This is an as yet largely unexplored avenue for the development of calorie restriction mimetic drugs that might recapture some of the benefits of eating less without the need to eat less:

Researchers have shown a new effect on aging via a small drug-like molecule that alters the perception of food in the nematode C. elegans. The researchers "tricked" the worm's metabolism into a state of caloric restriction, extending the animal's lifespan by 50 percent. The study provides a new avenue of inquiry for researchers around the world who are attempting to develop human drugs that mimic the positive effects of a Spartan diet. "This small molecule blocks the detection of food in the worm's mouth. The worm senses that its mouth is empty even when it is full of food, tricking the animal into shifting its physiology into a caloric restricted-state even when it's eating normally. Our study suggests that primary sensory pathways represent new targets for human pharmacology."

Researchers screened 30,000 synthetic, drug-like compounds in nematodes and identified several structurally related compounds that acted on mechanisms tied to caloric restriction. They found that the small molecule, NP1, impinged upon a food perception pathway by promoting glutamate signaling in the pharynx of the animal. The chemical activated a neurotransmitter-controlled food deprivation signal which altered the animal's normal metabolism into a caloric restriction state. Exploring sensory pathways as potential drug targets should be of interest to age researchers interested in mimicking caloric restriction in order to extend healthspan. The mechanisms involved in sensory pathways may be more specific than secondary pathways that detect energy levels or absorbed nutrients at the cellular level, such as the intracellular pathways mTOR and AMPK which are under study in many labs around the world. "Targeting sensory pathways may lead to a more rapid response to changing diet. Altering these higher level, specific response mechanisms may also have fewer effects on other systems in the body."

Link: http://www.eurekalert.org/pub_releases/2016-05/bifr-cwe052616.php


It would be interesting to know mutations affecting taste/smell affect longevity.

Posted by: Lou Pagnucco at May 30th, 2016 11:23 AM

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