WIKIMEDIA, DAN DICKINSON, GOLDSTEIN LAB, UNC CHAPEL HILL Food restriction boosts associative learning in nematode worms (Caenorhabditis elegans) by decreasing a neuromodulatory metabolite, according to a study published yesterday (August 1) in PLOS Biology.
Eating fewer calories produces numerous health benefits in animal and human models, including expanded longevity and heightened learning. However, it’s unclear whether these outcomes are mechanistically linked. In the current study, researchers sought to determine the molecular underpinnings of enhanced learning following a calorie-restricted diet and whether these same pathways were also responsible for promoting a longer lifespan.
Fasting improved performance in a task that required worms to learn an association between food and the scent of a pungent chemical. Worms who learned this association would choose to inch toward this chemical’s particular scent over alcohol.
The researchers demonstrated that fasting for an hour or a half hour decreases kynurenic acid, a product of the breakdown of L-tryptophan, with more robust effects after a longer fast. Higher levels of kynurenic acid can obstruct glutamate signaling within a group of neurons that regulate learning in this associative task in nematodes. By decreasing kynurenic acid without restricting food intake, the researchers also boosted the worms’ learning.
“[I]t remains to be determined whether kynurenic acid influences learning in mammals as directly as it does in worms, and whether manipulation of the pathway might offer new opportunities for therapeutic intervention in human disorders,” senior author Kaveh Ashrafi of the University of California, San Francisco, says in a news release.
In addition, the researchers demonstrated that key molecular pathways previously shown to be important for increased longevity also improve learning by dampening kynurenic acid. But, manipulating kynurenic acid levels didn’t affect the worms’ lifespans. Thus, the authors argue, the mechanisms by which dietary restriction increases lifespan and promotes learning are distinct.