“Why Do Females Live Longer than Males?” Search for the Responsible Genes in Drosophila Brain

In many animals, including humans, females tend to outlive males. The objective of this study is to identify the genes accountable for the sex-based differences in longevity. We conducted gene expression analyses in the brain using Drosophila as a model organism. Drosophila shares numerous genes with humans, and the brain governs diverse physiological functions while also significantly impacting lifespan. For this investigation, we utilized the white (BL#5905) strain raised at 25°C. The BL#5905 strain serves as the original parental line for numerous transgenic lines and is notable for being devoid of intestinal tumors, a prevalent cause of death in middle- and elder-aged Drosophila. We obtained the typical survival curve showing a 50% mortality rate occurring at 11.5 weeks post-eclosion (WPE) and a maximum lifespan of 17 WPE in females, while males were dead monotonically with aging up to 12 WPE. We dissected male brains at 1 and 10 WPE, following the same sampling schedule as for females. Additionally, females were sampled at 13 WPE, corresponding to a survival rate (~20%) observed at 10 WPE for males. To accommodate for circadian rhythm effects on gene expression, samples were collected every 4 hours, resulting in a total of 6 samples per day, within a light/dark cycle. Genome-wide expression profiles were generated via next-generation sequencing using total RNAs extracted from 50 to 110 brains per sample. We validated circadian fluctuations of known clock genes in both sexes, indicating the reliability of our data both qualitatively and quantitatively. This presentation will present preliminary findings, focusing on sex-specific differences in gene expression patterns with aging.