Fay and Carl Simmons Center for the Biology of Hearing and Deafness, Department of Otolaryngology, Washington University Medical School, 660 S. Euclid, St. Louis, MO 63110, USA.
Aging Dis. 2011 Jun;2(3):231-41. Epub 2011 Apr 28.
Age-related decline of cochlear function is mainly due to the loss of hair cells and spiral ganglion neurons (SGNs). Recent findings clearly indicate that survival of these two cell types during aging depends on genetic and environmental interactions, and this relationship is seen at the systemic, tissue, cellular, and molecular levels. At cellular and molecular levels, age-related loss of hair cells and SGNs can occur independently, suggesting distinct mechanisms for the death of each during aging. This mechanistic independence is also observed in the loss of medial olivocochlear efferent innervation and outer hair cells during aging, pointing to a universal independent cellular mechanism for age-related neuronal death in the peripheral auditory system. While several molecular signaling pathways are implicated in the age-related loss of hair cells and SGNs, studies with the ability to locally modify gene expression in these cell types are needed to address whether these signaling pathways have direct effects on hair cells and SGNs during aging. Finally, the issue of whether age-related loss of these cells occurs via typical apoptotic pathways requires further examination. As new studies in the field of aging reshape the framework for exploring these underpinnings, understanding of the loss of hair cells and SGNs associated with age and the interventions that can treat and prevent these changes will result in dramatic benefits for an aging population.
年龄相关性耳蜗功能下降主要归因于毛细胞和螺旋神经节神经元（SGN）的丧失。最近的研究结果清楚地表明，这两种细胞类型在衰老过程中的存活取决于遗传和环境的相互作用，这种关系可见于系统、组织、细胞和分子水平。在细胞和分子水平上，年龄相关性毛细胞和 SGN 的丧失可以独立发生，这表明在衰老过程中，每种细胞的死亡有不同的机制。这种机制的独立性也存在于衰老过程中内侧橄榄耳蜗传出神经纤维和外毛细胞的丧失中，这表明在周围听觉系统中，与年龄相关的神经元死亡存在一种普遍的独立的细胞机制。虽然有几种分子信号通路与年龄相关性毛细胞和 SGN 的丧失有关，但需要能够在这些细胞类型中局部修饰基因表达的研究，以确定这些信号通路在衰老过程中对毛细胞和 SGN 是否有直接影响。最后，还需要进一步研究这些细胞的衰老相关性丧失是否通过典型的凋亡途径发生。随着衰老领域的新研究重塑了探索这些潜在机制的框架，对与年龄相关的毛细胞和 SGN 丧失以及可以治疗和预防这些变化的干预措施的理解，将为老龄化人口带来显著的益处。
