Dietary Fatty Acids and Autophagy

The cellular housekeeping processes of autophagy show up everywhere in considerations of metabolism and aging: better repair of cellular damage and removal of unwanted metabolic byproducts has a noticeable beneficial effect on the longevity of an organism. Many of the genetic manipulations that extend life in laboratory species have been shown to enhance autophagy, just as does the practice of calorie restriction.

Here researchers find that the marginal benefits resulting from the inclusion of omega fatty acids in the diet may also result from increased autophagy:

Researchers have discovered that simple mutations in genetic pathways conserved throughout evolution can double or triple the lifespan of C. elegans and that similar mutations in the corresponding mammalian pathways also regulate lifespan. Many of these mutations also make animals resistant to starvation, suggesting that common molecular mechanisms may underlie both response to nutrient deprivation and the regulation of lifespan.

To find these mechanisms [scientists] searched genomic databases covering many types of animals for shared genes that respond to fasting by changing their expression. She found that expression of the C. elegans gene lipl-4 increases up to seven times in worms not given access to nutrients. A transgenic strain that constantly expresses elevated levels of lipl-4, even when given full access to food, was found to have increased levels of arachidonic acid (AA), an omega-6, and eicosapentanoic acid (EPA), an omega-3 fatty acid and to resist the effects of starvation.

Following the implication that omega fatty acids stimulate a process leading to starvation resistance, the researchers found that feeding AA and another omega-6 fatty acid, but not EPA, activated autophagy in non-transgenic C. elegans with full access to nutrients. Since activation of autophagy has been shown to increase lifespan in several genetic models, the authors tested the effect of omega-6 fatty acids on C. elegans lifespan and found that roundworms consuming a full normal diet supplemented with omega-6 fatty acids lived 20 to 25 percent longer than usual.

Since dietary supplementation with both omega-3 and omega-6 fatty acids has been shown to prevent or improve several human health conditions, the researchers tested the response of cultured human cells to omega fatty acid supplementation. As in C. elegans, the human cells responded to supplementation with the omega-6 acids, but not to EPA, by activation of autophagy, measured by levels of marker proteins. That result suggests that omega-6 acids induce autophagy across the full range of multicellular animal species. The researchers then showed that the lifespan-increasing properties of omega-6 fatty acids in C. elegans depend on the presence of genes required for autophagy.

Link: http://www.eurekalert.org/pub_releases/2013-02/mgh-crp021313.php

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