Scientists at the Salk Institute for Biological Studies found that boosting autophagy in the nervous system of fruit flies prevented the age-dependent accumulation of cellular damage in neurons and promoted longevity.
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. The research 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, 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.
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 that accumulate in neurons as normal part of the aging process,” says Dr. Simonsen, “but most importantly they demonstrate that enhancing the clearance of damaged proteins and protein aggregates increases longevity.”
The study will be reported in an upcoming issue of Autophagy.