According to the World Health Organization, one third of the population over 65 years old suffers from age-related hearing loss, also known as presbycusis, making it the second most common cause of disability in older people. IGF-1 is a neurotrophic factor fundamental for the regulation of cochlear development, growth and differentiation. Homozygous mutations in its encoding gene cause syndromic congenital neurosensorial deafness in mice and men. Patients with heterozygous IGF1 or IGF1R mutations do not present a clear hearing phenotype, but low levels of IGF-1 are associated with hearing loss and presbyacusis in related human syndromes (Varela-Nieto et al., 2013). Circulating IGF-1 levels decrease physiologically during mammalian aging, and this reduction has been related to human cognitive decline and neurodegeneration. Still the relationship between presbycusis and IGF-1 age-regulated levels has not been studied in depth. During the first year of life Igf1+/- mice suffered significant age-related hearing loss. Auditory thresholds and peak I latencies were measured by ABR and they increased with ageing alongside the decrease in the circulating levels of IGF-1. From the age of 6 months, Igf1+/- mice showed higher hearing thresholds and susceptibility to environmental stressors like noise when compared to wild type mice. Cochleae of Igf1+/- mice were studied by a combination of RT-qPCR and immunohistochemistry. Inflammatory pathways were further studied by using RNA arrays. IGF-1 partial deficit caused a chronic pro-inflammatory state in the cochlea. In turn, there is an exacerbated response to damage with increased IL6 levels, Iba1+ cellular infiltration and apoptotic cell death. In summary, genetic mouse models of human IGF-1 deficiency are a valuable tool to study the molecular bases of progressive hearing loss.

Resumen del póster presentado al MouseAGE Annual Meeting: "Preclinical interventions in ageing, frailty and multimorbidity", celebrado en Madrid (España) del 12 al 13 de abril de 2016.

This work was supported by EU FP7-PEOPLE TARGEAR (www.targear.eu) and Spanish SAF2014-53979-R. SP holds a Spanish FPI fellowship.

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