Rodríguez-de la Rosa Lourdes, Lassaletta Luis, Calvino Miryam, Murillo-Cuesta Silvia, Varela-Nieto Isabel
"Alberto Sols" Biomedical Research Institute CSIC-UAM, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto de Salud Carlos III, Madrid, Spain.
Front Aging Neurosci. 2017 Dec 12;9:411. doi: 10.3389/fnagi.2017.00411. eCollection 2017.
Aging is associated with impairment of sensorial functions and with the onset of neurodegenerative diseases. As circulating insulin-like growth factor 1 (IGF-1) bioavailability progressively decreases, we see a direct correlation with sensory impairment and cognitive performance in older humans. Age-related sensory loss is typically caused by the irreversible death of highly differentiated neurons and sensory receptor cells. Among sensory deficits, age-related hearing loss (ARHL), also named presbycusis, affects one third of the population over 65 years of age and is a major factor in the progression of cognitive problems in the elderly. The genetic and molecular bases of ARHL are largely unknown and only a few genes related to susceptibility to oxidative stress, excitotoxicity, and cell death have been identified. IGF-1 is known to be a neuroprotective agent that maintains cellular metabolism, activates growth, proliferation and differentiation, and limits cell death. Inborn IGF-1 deficiency leads to profound sensorineural hearing loss both in humans and mice. IGF-1 haploinsufficiency has also been shown to correlate with ARHL. There is not much information available on the effect of IGF-1 deficiency on other human sensory systems, but experimental models show a long-term impact on the retina. A secondary action of IGF-1 is the control of oxidative stress and inflammation, thus helping to resolve damage situations, acute or made chronic by aging. Here we will review the primary actions of IGF-1 in the auditory system and the underlying molecular mechanisms.
衰老与感觉功能受损以及神经退行性疾病的发生有关。随着循环胰岛素样生长因子1（IGF-1）的生物利用度逐渐降低，我们发现其与老年人的感觉障碍和认知表现直接相关。与年龄相关的感觉丧失通常是由高度分化的神经元和感觉受体细胞的不可逆死亡引起的。在感觉缺陷中，与年龄相关的听力损失（ARHL），也称为老年性聋，影响三分之一的65岁以上人群，并且是老年人认知问题进展的主要因素。ARHL的遗传和分子基础在很大程度上尚不清楚，仅鉴定出少数与氧化应激、兴奋性毒性和细胞死亡易感性相关的基因。已知IGF-1是一种神经保护剂，可维持细胞代谢、激活生长、增殖和分化，并限制细胞死亡。先天性IGF-1缺乏会导致人类和小鼠出现严重的感音神经性听力损失。IGF-1单倍体不足也已被证明与ARHL相关。关于IGF-1缺乏对其他人类感觉系统的影响，目前没有太多信息，但实验模型显示其对视网膜有长期影响。IGF-1的次要作用是控制氧化应激和炎症，从而有助于解决衰老导致的急性或慢性损伤情况。在此，我们将综述IGF-1在听觉系统中的主要作用及其潜在的分子机制。
