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Homeostatic maintenance and age-related functional decline in the Drosophila ear.

ABSTRACT: 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.

SUBMITTER: Keder A

PROVIDER: S-EPMC7198581 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Homeostatic maintenance and age-related functional decline in the Drosophila ear.

Keder Alyona A Tardieu Camille C Malong Liza L Filia Anastasia A Kashkenbayeva Assel A Newton Fay F Georgiades Marcos M Gale Jonathan E JE Lovett Michael M Jarman Andrew P AP Albert Joerg T JT

Scientific reports 20200504 1

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 ...[more]

PMID: 32366993

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Project description:Purpose Functional reserve represents the difference between an individual's ability to produce a maximum output function and the ability to perform a functional task. Several studies have documented an age-related decrease in functional reserve with oral tongue pressure generation. Whether this pattern is seen in pharyngeal swallowing pressures is unknown. The aim of this study was to investigate pharyngeal functional reserve using high-resolution manometry during normal-effort and effortful swallows. Method Pharyngeal high-resolution manometry was performed on 38 younger healthy individuals (≤ 40 years) and 18 older healthy individuals (≥ 60 years) during normal-effort and effortful water swallows. Pressure metrics included maximum pressure in the velopharynx, tongue base, and hypopharynx, as well as pharyngeal contractile integral and minimum pressure in the upper esophageal sphincter (UES). Repeated-measures analysis of variance was used to determine the effects of swallow task, age, and pharyngeal region on pressure generation. Results Maximum pharyngeal pressures and pharyngeal contractile integral were significantly increased during the effortful swallows compared to normal-effort swallows (p < .001), but there were no interactions between task and age in pharyngeal pressures. In the UES, minimum pressures were significantly elevated in older individuals during effortful swallows compared to normal-effort swallows (p = .007) but did not follow a pattern consistent with reduced functional reserve. Conclusions Healthy individuals increase pharyngeal driving pressures during effortful swallows, without an age-related reduction in the magnitude of pressure increase. Thus, this study did not find evidence for an age-related reduction in pharyngeal functional reserve. The preserved ability to increase pharyngeal pressures during effortful swallowing in aging may support the use of behavioral swallowing interventions in older individuals without neuromuscular conditions. Supplemental Material https://doi.org/10.23641/asha.16606709.

Dataset Information

Homeostatic maintenance and age-related functional decline in the Drosophila ear.

Publications

Homeostatic maintenance and age-related functional decline in the Drosophila ear.

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