Time Flies: Autophagy During Ageing in Drosophila

The process of ageing compromises the age-associated decrease in fertility, gradual loss of function, and increased vulnerability to disease, which progressively diminishes the capability of an organism to survive [1-3]. Unsurprisingly, in the past years it has been of great interest to understand which factors influence this inevitable and complex process. As a result a wide array of molecular and cellular damages has been identified and shown to accumulate during ageing. The lifelong accumulation of such damages will eventually result in frailty and disease [4]. The variety of identified age-dependent damages has given rise to different theories for molecular ageing mechanisms. These mechanisms include decreased cellular capacity to deal with DNA damage, and decline in cellular division capacity, which is linked to the progressive shortening of telomeres upon each cell cycle. Also an increased accumulation of damaged mitochondria and the involved increase in reactive oxygen species (ROS) production and decline in ATP synthesis has been shown to occur over time (reviewed in [5]). One of the phenotypic hallmarks of aged cells is the intracellular accumulation of damaged proteins and therefore protein turnover/protein degradation has attracted attention over the last years [2]. \n \nAt the same time, forward genetics have allowed to investigate single gene alterations and their influence on lifespan of whole organisms. Even though the ageing process is without doubt influenced by stochastic and environmental factors, single gene mutations were shown to extend lifespan in worms, flies, and mice, suggesting the existence of a central process of ageing [6, 7]. Many of the genetic manipulations that alter longevity affect metabolism, nutrient sensing and stress response pathways. As all these pathways are connected to autophagy(definition) (an important player also in protein turnover), the question about the role of autophagy in ageing has come more and more to the fore. In this chapter we will focus on how research conducted in the excellent genetic model system Drosophila melanogaster has contributed to understand more about the interplay of autophagy and ageing.