Fig. 1: Ubiquitous catalase upregulation extends lifespan in flies, independently of oxidative stress resistance.
From: Enhancing autophagy by redox regulation extends lifespan in Drosophila
a Constitutive, ubiquitous catalase over-expression (da-GAL4 > UAS-cat) extends the survival of female flies in a wDah (white Dahomey) WT background relative to the UAS-cat/+ (p = 5.7 × 10−7) and da-GAL4/+ (p = 3.3 × 10−6) controls. The control lines are not significantly different from each other (p = 0.7504). No effect is observed in males (p > 0.05 for all comparisons). Lifespans were performed with n = 200 flies per condition. b Inducible catalase over-expression from early adulthood (d2) using the GeneSwitch system extends the lifespan of female flies (da-GS > UAS-cat ± RU, p = 1.1 × 10−16). RU has no effect on the da-GS/+ control line (p = 0.7161). Lifespans were performed with n = 225–300 flies per condition. Inset: catalase over-expression assessed by Western blotting in whole d9 females ( = d7 of RU induction), with actin as a loading control. c Healthspan, inferred from climbing performance, is improved in catalase over-expressing females. Climbing was assayed on da-GS > UAS-cat females ± RU to control for effects of eye colour on this behaviour. Data are presented as box-and-whisker plots (interquartile range, line at median, min/max error bars) of n = 5 replicates per condition, each with n = 15 flies per sample, analysed by unpaired two-tailed Student’s t-test. d Mortality trajectories of the da-GS > UAS-cat ± RU survival curves from (b), fitted with a linear regression trendline (dotted line). e Late onset over-expression of catalase using the inducible GeneSwitch system from either middle-age (d28 and d42) and old-age (d56) extends the lifespan of female flies (p = 7.2 × 10−8, p = 1.0 × 10−7 and p = 1.4 × 10−3, respectively against the −RU control). Lifespans were performed with n = 270 flies per condition, and were plotted from point of RU induction relative to the remaining −RU control flies at that age (see Supplementary Fig. 1l for the full survival data). f Catalase over-expressing flies are strongly resistant to exogenous H2O2 stress relative to controls (da-GAL4 > UAS-cat v. UAS-cat/+; p = 5.0 × 10−61 females, p = 3.2 × 10−33 males). H2O2 treatment (5% v/v in sucrose/agar medium) was initiated at d7, with n = 105 males (n = 75 for da-GS > UAS-cat) and n = 120 females per condition. g Catalase over-expressing flies are resistant to chronic dietary paraquat stress relative to control flies (da-GAL4 > UAS-cat v. UAS-cat/+; p = 6.93 × 10−31 females, p = 7.99 × 10−16 males). Paraquat treatment (20 mM in SYA food) was initiated at d7, with n = 100 flies per condition. h Catalase over-expressing flies (da-GAL4 > UAS-cat) are resistant to acute paraquat stress relative to controls (UAS-cat/+). d7 females were injected with 75 nL of 1 mg/mL paraquat in Ringers buffer (+ PQ, n = 150 flies) or mock injected with buffer alone (−PQ, n = 120 flies). i Catalase over-expressing flies are resistant to environmental hyperoxia stress relative to controls (da-GAL4 > UAS-cat v. UAS-cat/+; p = 1.7 × 10−8 females, p = 8.1 × 10−3 males). Incubation at 90% O2 was initiated at d7, with n = 120 flies per condition (except n = 90 for UAS-cat/+ females). All survival assays (a, b, e, f, g, i) were analysed by Log-Rank test (see Supplementary Data 1 for full n numbers and p values). n/s, p > 0.05; *, p < 0.05; **, p < 0.01; ***, p < 0.001. Source data are provided as a Source Data file.
