Insulin-like growth factor 1 deficiency and hearing loss

Abstract

Insulin like growth factor 1 (IGF-1) plays a central role in embryonic development and adult tissue homeostasis. Accordingly, it is an essential factor for the regulation of cochlear development through controlling apoptosis and late neuronal differentiation. In the cochlea, IGF-1 actions are mediated by a network of protein kinases (RAF, AKT and p38 MAPK) that modulate the expression and activity of transcription factors (AP1, MEF2, FoxG1 and FoxM1) leading to the regulation of cell cycle and metabolism. IGF-1deficiency causes hearing loss in mice and men, whereas low serum levels of IGF-1are associated with human syndromes showing hearing lossand with premature presbyacusis. Animal models are fundamental to understand the genetic, epigenetic, and environmental factors that contribute to human hearing loss. Mouse IGF-1 plasmatic levels decrease with ageing, concomitantly hearing loss and retinal degeneration occur, in a normal ageing process that is accelerated in the heterozygous Igf1-/+mouse.Furthermore, low IGF-1 levels predispose to increased damage after noise-exposure. In the Igf1 null mouse, hearing-loss is caused byearly neuronal loss and age-related stria vascularis alterations. In summary, our data suggest that serum IGF-1 levels could be a novel diagnostic tool for hearing loss and support the hypothesis that IGF-1-based treatments have potential for the protection or repair of hearing loss.