Priority Research Paper Volume 1, Issue 8 pp 699—713

Increased uncoupling protein (UCP) activity in Drosophila insulin-producing neurons attenuates insulin signaling and extends lifespan

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Figure 3. Targeted UCP expression in the adult IPCs extends life span and renders flies stress resistant with normal fecundity. Survivorship curves for female (A) and male (B) flies are shown. Two independent trials were performed and results from one trial are shown for one hUCP2 and two mUCP1 lines. Gray lines are control dilp2-Gal4/w1118 flies; two mUCP1 expressing dilp2-Gal4/UAS-mucp1 lines, mUCP1A and mUCP1B are green and red lines, respectively; and orange lines are dilp2-Gal4/UAS-hucp2. Panel A (females) median life spans are 55 for controls and 71, 63, and 65 for three UCP transgenic lines. Panel B (male) median life spans are 57 for controls and 70, 59, and 59 for three UCP transgenic lines. Log rank analysis shows an average of 19% increase in median life span in female with targeted UCP expression in the adult IPCs and an average of 10% increase in male (see SI Supplementary Table 1). (C) Female fecundity is similar for flies expressing mUCP1 or hUCP2 in the adult IPCs and control flies. Average number of eggs per day for 20 individual females was determined from daily counts of eggs produced from single mated pairs [6]. (D) Transgenic flies with targeted UCP expression in the adult IPCs are resistant to oxidative stress. Survival during administration of paraquat (20 mM paraquat in 5% sucrose) shows that 10-day-old flies expressing mUCP1 or hUCP2 in the IPCs are more resistant than controls. (E) mUCP1 or hUCP2-expressing flies are resistant to starvation. Ten-day-old dilp2-Gal4/UAS-mucp1 and dilp2-Gal4/UAS-hucp2 flies were placed in vials containing water soaked filters and the number of dead flies was counted at noted time intervals. Three independent assays were performed and a representative experiment is shown for females. All values are presented as mean ± S.E.M. Similar differences were seen for males and females. Each experiment included 8-10 vials with 20 flies in each vial, total of 160-200 flies for each condition.