Fig. 3.
Effects of dfoxo removal on the survivorship of IIS-compromised flies. (A) Survival curves of female flies overexpressing a dominant negative version of the insulin receptor (daGAL > UAS-InRDN) and their genetic controls (daGAL/+ and UAS-InRDN/+) in both wild-type and dfoxo− backgrounds (representative of two independent experiments). In a wild-type background: for daGAL > UAS-InRDN median survival = 71 days, maximum survival = 82 days, n = 93; for daGAL/+ median survival = 61 days, maximum survival = 77 days, n = 114; for UAS-InRDN/+ median survival = 64 days, maximum survival = 75, n = 115. The survival of daGAL > UAS-InRDN flies was significantly different from each of the controls (P <0.0001; log-rank test). No significant difference in survival was detected between the two controls (P = 0.6, log-rank test). In a dfoxo− background: for daGAL > UAS-InRDN median survival = 53 days, maximum survival = 64 days, n = 114; for daGAL/+ median survival = 49 days, maximum survival = 59 days, n = 109; for UAS-InRDN/+ median survival = 49 days, maximum survival = 57 days, n = 106. The survival of daGAL > UAS-InRDN dfoxo− flies is significantly different from each of the controls (P <0.001; log-rank test). No significant difference in survival was detected between the two controls (P = 0.5, log-rank test). (B) Survival curves of female flies with late ablation of the median neurosecretary cells (InsP3GAL > UAS-rpr) and their genetic controls (InsP3GAL/+ and UAS-rpr/+) in both wild-type and dfoxo− backgrounds. In a wild-type background: for InsP3GAL > UAS-rpr median survival = 82 days, maximum survival = 100 days, n = 99; for InsP3/+ median survival = 60 days, maximum survival = 82 days, n = 94; for UAS-rpr/+ median survival = 62 days, maximum survival = 82 days, n = 93. The survival of InsP3GAL > UAS-rpr flies was significantly different from each of the controls (P <10−12, log-rank test). No significant difference in survival was detected between the two controls (P = 0.8, log-rank test). In a dfoxo− background: for InsP3GAL > UAS-rpr median survival = 44 days, maximum survival = 58 days, n = 94; for InsP3/+ median survival = 41 days, maximum survival = 56 days, n = 108; for UAS-rpr/+ median survival = 44 days, maximum survival = 59 days, n = 95. The survival of InsP3GAL > UAS-rpr flies was not significantly different from either of the controls (P>0.2, log-rank test). (C) Survival curves of female daGS > UAS-InRDN flies induced to ubiquitously express the dominant negative insulin receptor by feeding RU486-containing food from day 3 of adulthood (wild-type +RU486: median survival = 83 days, maximum survival = 95 days, n = 94; dfoxo− +RU486: median survival = 46 days, maximum survival = 70 days, n = 81) compared with uninduced controls (wild-type −RU486: median survival = 67 days, maximum survival = 90 days, n = 97; dfoxo−−RU486: median survival = 44 days, maximum survival = 65 days, n = 79). The survival of wild-type daGS > UAS-InRDN +RU486 was significantly different from the −RU486 control (P <10−6, log-rank test). The survival of dfoxo− daGS > UAS-InRDN +RU486 was not significantly different from the −RU486 control (P = 0.2, log-rank test). (D) Survival curves of female daGS > UAS-dp110DN flies induced to ubiquitously overexpress a dominant negative form of Dp110 by feeding RU486-containing food from day 3 of adulthood (wild-type +RU486: median survival = 80 days, maximum survival = 97 days, n = 91; dfoxo− +RU486: median survival = 51 days, maximum survival = 65 days, n = 95) compared with uninduced controls (wild-type −RU486: median survival = 75 days, maximum survival = 92 days, n = 103; dfoxo−−RU486: median survival = 54 days, maximum survival = 65 days, n = 97). The survival of wild-type daGS > UAS-dp110DN +RU486 was significantly different from the −RU486 control (P<0.001, log-rank test). The survival of dfoxo− daGS > UAS-dp110DN +RU486 was not significantly different from the −RU486 control (P = 0.4, log-rank test). Representative of two independent experiments.