Age-related hearing loss (ARHL) is a threat to future human wellbeing. Multiple factors contributing to the terminal auditory decline have been identified; but a unified understanding of ARHL-or the homeostatic maintenance of hearing before its breakdown-is missing. We here present an in-depth analysis of homeostasis and ageing in the antennal ears of the fruit fly Drosophila melanogaster. We show that Drosophila, just like humans, display ARHL. By focusing on the phase of dynamic stability prior to the eventual hearing loss we discovered a set of evolutionarily conserved homeostasis genes. The transcription factors Onecut (closest human orthologues: ONECUT2, ONECUT3), Optix (SIX3, SIX6), Worniu (SNAI2) and Amos (ATOH1, ATOH7, ATOH8, NEUROD1) emerged as key regulators, acting upstream of core components of the fly's molecular machinery for auditory transduction and amplification. Adult-specific manipulation of homeostatic regulators in the fly's auditory neurons accelerated-or protected against-ARHL.

By beating their wings faster around sunset, male Anopheles mosquitoes sensitize their auditory system to female flight tones.

Background Release of gene-drive mutants to suppress Anopheles mosquito reproduction is a promising method of malaria control. However, many scientific, regulatory and ethical questions remain before transgenic mosquitoes can be utilised in the field. At a behavioural level, gene-drive carrying mutants should be at least as sexually attractive as the wildtype populations they compete against, with a key element of Anopheles copulation being acoustic courtship. We analysed sound emissions and acoustic preference in a doublesex mutant previously used to collapse Anopheles gambiae (s.l.) cages. Methods Anopheles rely on flight tones produced by the beating of their wings for acoustic mating communication. We assessed the impact of disrupting a female-specific isoform of the doublesex gene (dsxF) on the wing beat frequency (WBF; measured as flight tone) of males (XY) and females (XX) in homozygous dsxF− mutants (dsxF−/−), heterozygous dsxF− carriers (dsxF+/−) and G3 dsxF+ controls (dsxF+/+). To exclude non-genetic influences, we controlled for temperature and wing length. We used a phonotaxis assay to test the acoustic preferences of mutant and control mosquitoes. Results A previous study showed an altered phenotype only for dsxF−/− females, who appear intersex, suggesting that the female-specific dsxF allele is haplosufficient. We identified significant, dose-dependent increases in the WBF of both dsxF−/− and dsxF+/− females compared to dsxF+/+ females. All female WBFs remained significantly lower than male equivalents, though. Males showed stronger phonotactic responses to the WBFs of control dsxF+/+ females than to those of dsxF+/− and dsxF−/− females. We found no evidence of phonotaxis in any female genotype. No male genotypes displayed any deviations from controls. Conclusions A prerequisite for anopheline copulation is the phonotactic attraction of males towards female flight tones within mating swarms. Reductions in mutant acoustic attractiveness diminish their mating efficiency and thus the efficacy of population control efforts. Caged population assessments may not successfully reproduce natural mating scenarios. We propose to amend existing testing protocols to better reflect competition between mutants and target populations. Our findings confirm that dsxF disruption has no effect on males; for some phenotypic traits, such as female WBFs, the effects of dsxF appear dose-dependent rather than haplosufficient.