PERSPECTIVE daf-41/p23: A Small Protein Heating Up Lifespan Regulation

The life span of non-renewing organisms is determined by the potential of their individual cells to maintain their functions while aging. Nematodes, like Caenorhabditis elegans with their 20 days of adult life, have proven to be excellent model systems to study organismal lifespan, its variability, and its regulation [1–3]. Early on, the life span could be linked to environmental conditions, like growth temperature and food intake [1,4]. In general, in these experiments, organisms develop and age slower and live longer at lower growth temperatures. This is evident from a clear relation-ship between temperature and life span ranging from 35 days to 9 days upon temperature changes from 10 to 25.5 degrees [1]. On the higher end of this temperature range, C. elegans can enter the dauer state, which is also found in response to starvation or the presence of dauer pheromone [5– 7]. The formation of this stress-resistant state, which enables survival of the organism for longer than 3 months, requires morphological changes to the cuticule and inhibition of further develop-ment. Interestingly, it is entirely reversible without effects on the later adult life span [8]. This deci-sion has been analyzed genetically in detail, identifying genes that promote dauer entry (DAF-c) and those that prevent dauer entry (DAF-d). These studies unravel the pathways, which cooperate in the decision whether to enter the path to the dauer state instead of normal development. Th