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Aging gracefully requires taking out the trash
Date:12/14/2007

aging, says Finley. This may be particularly important in the nervous system since neurons produce damaged molecules at a much higher rate than most cell types. Keeping cells free of damaged molecules is critical for neurons because unlike many cells, they do not divide or replace themselves once created at birth. They rely on autophagy together with other clearance and detoxification pathways to keep themselves healthy and functioning for decades, explains Finley.

For their studies, the Salk researchers turned to the fruit fly Drosophila, a powerful model organism, whose genetics can easily be manipulated. When initial experiments indicated that the expression of several autophagy genes decreased over the normal lifespan of fruit flies, the Salk researchers focused on one particular protein, Atg8a. This protein is an essential component needed for the formation of new autophagosomes. Finley and her team found that levels of Atg8a were significantly reduced by four weeks of age, a time when the flies are considered middle aged. At the same time, protein aggregates were not efficiently cleared by the cellular clean-up crew and started to accumulate.

Without Atg8a, things went from bad to worse. Damaged proteins tagged for degradation started to pile up early and life expectancy plummeted. The abnormal accumulation of protein aggregates had striking similarities to those seen in the most common human neurodegenerative diseases, says first author Anne Simonsen, Ph.D., a visiting scientist from the University of Oslo, Norway.

When the researchers kept the neuronal levels of Atg8a high, the genetically engineered flies were spared the ravages of time. Promoting the pathway not only prevented the accumulation of protein aggregates but also significantly extended the average lifespan. Our experiments show for the first time genetically that autophagy can sequester and eliminate misfolded and damaged proteins, which accumulate in neurons as no
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Contact: Gina Kirchweger
Kirchweger@salk.edu
858-453-4100 x1340
Salk Institute  
Source:Eurekalert

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