2024-03-29T05:07:24Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1541672018-10-03T09:40:39Zcom_10261_22com_10261_1col_10261_401
The role of insulin-like growth factor 1 (IGF-1) deficiency in the progression of age-related hearing loss
Celaya, Adelaida M.
Murillo-Cuesta, Silvia
Rodriguez-de la Rosa, Lourdes
Pulido, Sara
Varela-Nieto, Isabel
Ministerio de Economía y Competitividad (España)
European Commission
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.
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.
2017-08-17T12:32:11Z
2017-08-17T12:32:11Z
2016
2017-08-17T12:32:13Z
póster de congreso
MouseAGE Annual Meeting (2016)
http://hdl.handle.net/10261/154167
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100000780
eng
Sí
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-53979-R
info:eu-repo/grantAgreement/EC/FP7/612261
closedAccess