Sensory perception of dead conspecifics induces aversive cues and modulates lifespan through serotonin in Drosophila

Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. We found that in the vinegar fly, Drosophila melanogaster, exposure to dead conspecifics in the environment induced cues that were aversive to other flies, modulated physiology, and impaired longevity. The effects of exposure to dead conspecifics on aversiveness and lifespan required visual and olfactory function in the exposed flies. Furthermore, the sight of dead flies was sufficient to produce aversive cues and to induce changes in the head metabolome. Genetic and pharmacologic attenuation of serotonergic signaling eliminated the effects of exposure on aversiveness and lifespan. Our results indicate that Drosophila have an ability to perceive dead conspecifics in their environment and suggest conserved mechanistic links between neural state, health, and aging; the roots of which might be unearthed using invertebrate model systems.

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All flies for all experiments were randomized to treatment vials using our DLife survival analysis software or by generating random numbers in the statistical package R (e.g., runif) and then using those random numbers to assign animals and genotypes to treatments and vials.
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For all preference assays, P-values comparing the Preference Index among treatments was obtained using a randomization procedure and the statistical software R. Briefly, the null distribution of no difference among treatments was obtained by randomizing individual preference indices obtained from groups of 20 flies among all measures (maintaining block structure when appropriate) and 100,000 tstatistics (or F statistics for multiple comparisons). P-values (one-sided or two-sided as appropriate) were determined by computing the fraction of null values that were equal or more extreme to the observed t-statistic (or F-statistic). Mean preference values were plotted and weighted by the number of choosing flies in each trial, with the error bars representing the standard error of the mean. Experimentwise error rates for experiments comparing three or more treatments were protected by presentation of treatment P-value from nonparametric, randomization ANOVA, which are reported in the Figure Legends when appropriate. For lifespan and starvation assays, we employed survival analysis. Unless otherwise indicated, group-and pairwise-comparisons among survivorship curves (both lifespan and starvation) were performed using the DLife computer software and the statistical software R. P-values were obtained using log-rank analysis (select pairwise comparisons and group comparisons or interaction studies) as noted. Interaction P-values were calculated using Cox-Regression when the survival data satisfied the assumption of proportional hazards. In other cases (as noted in the figure legends), we used ANOVA to calculate P-values for the interaction term for age at death. For all box plots, the box represents Standard Error of the Mean (SEM, centered on the mean), and whiskers represent 10%/90%. For CO2, TAG, and negative geotaxis measures, P-values were obtained by standard two-sided t-test after verifying normality and equality of variances.

October 2018
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