2 Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, United States
- At lower temperature (15°C), the daf-2(e1370) mutants are long-lived to the same extent as at higher temperatures (Figure 1). In addition, at lower temperature (15°C) daf-2(e1370) mutants are also stress resistant (Gems et al. 1998).
- The transcription factors DAF-16 and SKN-1 that are phosphorylated directly by IIS, and thereby prohibited from entering the nucleus, are nuclear in daf-2(e1370) mutants at 15°C to the same extent as at higher temperatures (Lin et al. 2001 PMID:11381260; Tullet et al. 2008; Ewald et al. 2015).
These findings suggest that IIS is reduced comparably at 15°C and 25°C and argues against the assumption that e1370 is necessarily a temperature-sensitive allele in the classic sense where temperature affects protein folding and activity. Interestingly, about 10% wild-type worms form dauers when grown at 27°C under otherwise standard culturing conditions (ample food and not overcrowded; (Ailion & Thomas 2000 PMID:11063684)). Furthermore, it has been observed that null mutants in other abnormal-DAuer-Formation (daf) genes than daf-2, only show the dauer phenotype at higher temperatures, suggesting that the dauer phenotype itself is temperature sensitive. This observation was published over 30 years ago (Golden & Riddle 1984) and is discussed in (Wood 1988).
We are motivated to write to the WBG community by the assumption that during adulthood daf-2(e1370) mutants improperly reactive phenotypes that are reminiscent of dauer larvae (reduced mobility, reduced brood-size, short body size; (Gems et al. 1998)). Recently, we have shown that daf-2(e1370) mutants form dauers independent of SKN-1/NRF1,2,3 and that SKN-1 is only required for the daf-2(e1370)-longevity phenotype when these dauer-related phenotypes are not activated during adulthood (Ewald et al. 2015). Furthermore, comparing expression profiles of daf-2(e1370) mutants with dauer larvae revealed that they share only a common overlap under conditions that reactivate these dauer phenotypes (e.g., daf-2(e1370) at higher but not at lower temperatures; (Ruzanov et al. 2007 PMID:17543485; McElwee et al. 2004 PMID:15308663; Ewald et al. 2015)). Finally, treating wild-type worms with dauer pheromone was sufficient to increase lifespan (Kawano et al. 2005 PMID:16377915; Ewald et al. 2015). This suggests that there might be a dauer program activated in daf-2(e1370) mutants at higher temperatures that masks other underlying mechanisms of reduced IIS on lifespan. Further research is required, however, these findings suggest that reduced IIS can extend lifespan via dauer-dependent and dauer-independent mechanisms and this changes the interpretation of experiments performed with daf-2(e1370) mutants under conditions that promote these dauer-associated phenotypes.
Golden, J.W. & Riddle, D.L., 1984. A pheromone-induced developmental switch in Caenorhabditis elegans: Temperature-sensitive mutants reveal a wild-type temperature-dependent process. Proceedings of the National Academy of Sciences of the United States of America, 81(3), pp.819–823.
Wood, W.B. ed., 1988. The Nematode Caenorhabditis elegans. 1st ed., Cold Spring Harbor Monograph Series.