title: A comparative study of age-related hearing loss in wild type and insulin-like growth factor I deficient mice.
abstract: Insulin-like growth factor-I (IGF-I) belongs to the family of insulin-related peptides that fulfils a key role during the late development of the nervous system. Human IGF1 mutations cause profound deafness, poor growth and mental retardation. Accordingly, Igf1(-/-) null mice are dwarfs that have low survival rates, cochlear alterations and severe sensorineural deafness. Presbycusis (age-related hearing loss) is a common disorder associated with aging that causes social and cognitive problems. Aging is also associated with a decrease in circulating IGF-I levels and this reduction has been related to cognitive and brain alterations, although there is no information as yet regarding the relationship between presbycusis and IGF-I biodisponibility. Here we present a longitudinal study of wild type Igf1(+/+) and null Igf1(-/-) mice from 2 to 12 months of age comparing the temporal progression of several parameters: hearing, brain morphology, cochlear cytoarchitecture, insulin-related factors and IGF gene expression and IGF-I serum levels. Complementary invasive and non-invasive techniques were used, including auditory brainstem-evoked response (ABR) recordings and in vivo MRI brain imaging. Igf1(-/-) null mice presented profound deafness at all the ages studied, without any obvious worsening of hearing parameters with aging. Igf1(+/+) wild type mice suffered significant age-related hearing loss, their auditory thresholds and peak I latencies augmenting as they aged, in parallel with a decrease in the circulating levels of IGF-I. Accordingly, there was an age-related spiral ganglion degeneration in wild type mice that was not evident in the Igf1 null mice. However, the Igf1(-/-) null mice in turn developed a prematurely aged stria vascularis reminiscent of the diabetic strial phenotype. Our data indicate that IGF-I is required for the correct development and maintenance of hearing, supporting the idea that IGF-I-based therapies could contribute to prevent or ameliorate age-related hearing loss.
authors.affiliation: Instituto de Investigaciones Biomedicas "Alberto Sols", CSIC-UAM Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Riquelme
authors.forename: Rafael
authors.initials: R
authors.lastname: Cediel
authors.forename: Julio
authors.initials: J
authors.lastname: Contreras
authors.forename: Rodriguez-de
authors.initials: RD
authors.lastname: la Rosa Lourdes
authors.forename: Silvia
authors.initials: S
authors.lastname: Murillo-Cuesta
authors.forename: Catalina
authors.initials: C
authors.lastname: Hernandez-Sanchez
authors.forename: Jose M
authors.initials: JM
authors.lastname: Zubeldia
authors.forename: Sebastian
authors.initials: S
authors.lastname: Cerdan
authors.forename: Isabel
authors.initials: I
authors.lastname: Varela-Nieto