A) Nicotine-treated (24 μM) control flies that do not express Sph-1 (UAS-Sph-1/+; +) show reduced life expectancy compared to non-treated animals. B) Flies that express Sph-1 in dopaminergic neurons (UAS-Sph-1/+; +) have a reduced life expectancy that is rescued by nicotine treatment. C) In flies that express Sph-1 in their serotonergic system (UAS-Sph-1/+; UAS-tph-GAL4/+), the effect of nicotine on life span is smaller; however, this chemical significantly extends life expectancy, particularly at older ages (around 80 days). D) When Sph-1 is expressed in both the dopaminergic and serotonergic systems (UAS-Sph-1/+; UAS-ddc-GAL4/+), nicotine treatment promotes survival in a similar manner to that observed in flies expressing Sph-1 only in the dopaminergic system. The most evident effect is in flies aged over 60 days. Whole lifespan significance was evaluated using the Mantel-Cox test. Asterisks denote significance between untreated (black lines) and treated (red lines) groups, *** P < 0.001, **** P < 0.0001; n = 100 animals per group. Significant differences at half-lives (asterisks over the vertical dotted line) were assessed using Fisher’s exact test. Control P = 0.0142, TH P = 0.0374, TPH P = 0.3091, DDC P = 0.882.