Researchers from the Buck Institute have pinpointed a small molecule, similar to a drug, which changes the body’s attitude towards food within a type of worm known as C. elegans. Researchers used their new knowledge to trick the metabolism within the worm to restrict calories, which in turn increased the lifespan of the animal by 50 percent. Calorie restriction has been shown to extend lifespans as well as healthspans in mice and other simple animals. Researchers would like to use this research to extend this benefits to humans.
Senior author Gordon Lithgow says this small molecule works to block the detection of food within the mouth of the worm. The worm believes its mouth is empty even when it is full of food, causing it to change its physiology into a restricting state even when it’s eating regularly. The study suggests primary sensor pathways represent new targets for human pharmacology.
Lead author Mark Lucanic has screened 30,000 synthetic, drug-like components in nematodes and located many compounds that are structurally similar and act on mechanisms that are in a caloric restriction state. He discovered that a molecule known as NP1 promoted glutamate signaling inside the pharynx of animals, disturbing perception of food. The chemical activated a food deprivation signal controlled by a neurotransmitter, changing the metabolism from a regular state to a restricted one.
Lithgow says the next phase in the work is to focus on a better understanding of sensory pathways that may hold the potential to become drug targets that will artificially lead to mimicked caloric restricting. Lithgow states the mechanisms that work inside sensory pathways may be more than mere secondary pathways that track energy levels or nutrient absorption levels on a cellular level. When sensory pathways are targeted, this could lead to diet changes more rapid than ever before. This could also cause fewer effects on other systems throughout the body as changes are made.
Lucanic plans to work on identifying the molecule that NP1 activates within the sensory pathway. He will also take a deeper look at synthetic compounds that he picked up as being aging pathways during his screening process. Large amounts of both natural and synthetic compounds which directly affect aging have been found within simple animals, and that deeper exploration is required in order to pinpoint cause and effect to help extend the healthspan of the human species.
The complete research was published within the Aging Cell journal.