Cellular renewal process may underlie benefits of omega fatty acids

A search for genes that change their levels of expression in response to nutrient deprivation has uncovered potential clues to the mechanism underlying the health benefits of omega fatty acids. In the Feb. 15 issue of Genes & Development, Massachusetts General Hospital (MGH) researchers describe finding that feeding omega-6 fatty acids to C. elegans roundworms or adding them to cultured human cells activates a cellular renewal process called autophagy, which may be deficient in several important diseases of aging. A process by which defective or worn-out cellular components and molecules are broken down for removal or recycling, autophagy is also activated in metabolically stressful situations, allowing cells to survive by self-digesting nonessential components.

"Enhanced autophagy implies improved clearance of old or damaged cellular components and a more efficient immune response," says Eyleen O’Rourke, PhD, of MGH Molecular Biology, lead author of the report. "It has been suggested that autophagy can extend lifespan by maintaining cellular function, and in humans a breakdown in autophagic function may involved in diseases including inflammatory bowel disease, Parkinson’s disease, and in a more complex way in cancer and metabolic syndrome."

O’Rourke is a research fellow in the laboratory of MGH investigator Gary Ruvkun, PhD, whose team investigates the development, longevity and metabolism of C.elegans. Ruvkun and other 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 O’Rourke 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.

(Image: The Herman Lab, Kansas State University)