Fig. 4. Aging and physiology are modulated by neural mechanisms of expectation and reward.

(A) Inhibition of npf-expressing neurons abrogates differences in starvation caused by pheromone exposure. N = 43 and 45 for control (npf-GAL4;w¹¹¹⁸) flies exposed to male or female donor pheromones, respectively (P = 0.005 by log-rank test). N = 48 and 47 for treatment (npf-GAL4; UAS-shi^ts) flies exposed to male or female donor pheromones, respectively (P = 0.50 by log-rank test). (B) Activation of npf-expressing neurons causes decreased longevity in the absence of pheromone exposure. UAS-dTrpA1/+; npf-GAL4/+ males (N=239) exhibit significantly shorter lifespan compared to UAS-dTrpA1/+ (N=235; p≤0.001 by log-rank test) and npf-GAL4/+ (N=179; p≤0.001 by log-rank test) male transgene controls. (C) Mortality rates are reduced when males exposed to female donor pheromone (dashed black line) are given access to excess females (dashed red line; P=0.02 through 20 days of age by Aalen regression). Cohorts consisted of five experimental males together with either (i) 30 control donor males (solid black), (ii) 30 feminized donor males (dashed black), (iii) 5 feminized donor males + 25 females (dashed red), or (iv) 5 control donor males + 25 females (solid red). 20 replicate cohorts, totaling 100 experimental flies, were measured for each treatment. (D) Significantly enriched Gene Ontology pathways and functions whose genes are differentially regulated following pheromone exposure. A complete list of genes with significant changes in expression is provided in Table S1.