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Research Paper

Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila

Anne Simonsen, Robert C. Cumming, Andreas Brech, Pauline Isakson, David R. Schubert and Kim D. Finley

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Autophagy is involved with the turnover of intracellular components and the management of stress responses. Genetic studies in mice have shown that suppression of neuronal autophagy can lead to the accumulation of protein aggregates and neurodegeneration. However, no study has shown that increasing autophagic gene expression can be beneficial to an aging nervous system. Here we demonstrate that expression of several autophagy genes is reduced in Drosophila neural tissues as a normal part of aging. The age-dependent suppression of autophagy occurs concomitantly with the accumulation of insoluble ubiquitinated proteins (IUP), a marker of neuronal aging and degeneration. Mutations in the Atg8a gene (autophagy-related 8a) result in reduced lifespan, IUP accumulation and increased sensitivity to oxidative stress. In contrast, enhanced Atg8a expression in older fly brains extends the average adult lifespan by 56% and promotes resistance to oxidative stress and the accumulation of ubiquitinated and oxidized proteins. These data indicate that genetic or age-dependent suppression of autophagy is closely associated with the buildup of cellular damage in neurons and a reduced lifespan, while maintaining the expression of a rate-limiting autophagy gene prevents the age-dependent accumulation of damage in neurons and promotes longevity.

Authors

Anne Simonsen

The Norwegian Radium Hospital

Robert C. Cumming

The Salk Institute for Biological Studies

Andreas Brech

Cancer Institute, Norwegian Radium Hospital

Pauline Isakson

The Norwegian Radium Hospital

David R. Schubert

The Salk Institute for Biological Studies

Kim D. Finley

The Salk Institute for Biological Studies

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.