Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

Aging (Albany NY). 2016 Sep 23;8(9):2081-2099. doi: 10.18632/aging.101045.

Abstract

Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL.

Keywords: aging; auditory system; drug discovery; hearing loss; neurodegeneration; neuroscience.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / pathology*
  • Aging / physiology
  • Aldosterone / pharmacology*
  • Aldosterone / therapeutic use
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Auditory Threshold / drug effects*
  • Auditory Threshold / physiology
  • Mice
  • Neurons / drug effects*
  • Neurons / pathology
  • Presbycusis / drug therapy*
  • Presbycusis / pathology
  • Presbycusis / physiopathology
  • Receptors, Mineralocorticoid / metabolism
  • Spiral Ganglion / drug effects*
  • Spiral Ganglion / pathology
  • Spiral Ganglion / physiopathology

Substances

  • Receptors, Mineralocorticoid
  • Aldosterone