Description
Autophagy, Greek for self-eating, is involved with the breakdown of damaged cellular contents, such as damaged organelles or proteins aggregates, to supply the building blocks for new components. We have shown that defects in the autophagy pathway result in reduced lifespans, premature aging, and the build-up of neural protein aggregates and neural degeneration in Drosophila. In humans, many age-dependent neurodegenerative diseases are associated with the build-up of protein aggregates. Mutations in autophagy genes, such as the Atg8a gene in Drosophila, results in flies with reduced longevity and accelerated insoluble ubiquitinated protein (IUP) accumulation. Defects in the insulin-signaling pathway, such as mutations in chico, the insulin receptor substrate, promote increased basal rates in autophagy, enhance longevity, and reduce neural IUP accumulation. A non-genetic intervention on aging is through intermittent fasting (IF); studies across multiple species indicate that IF increases lifespan. Therefore, we are interested in characterizing the molecular pathways that sense nutrition and have a profound effect on cellular aging. The goal of this study is to examine the role of nutrition, insulin-signaling, autophagy, and aging in Drosophila. This work has implications for human health, including risk factors like Type II Diabetes and Metabolic Syndrome. The results of this work suggest that IF may be an effective preventative treatment to sow or prevent progressive neurodegenerative disorders such as Parkinson's or Alzheimer's diseases.
