Department of Otorhinolaryngology, Smell and Taste Clinic, University of Dresden Medical School, Dresden, Germany.
Department of Developmental, Molecular, and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA.
J Comp Neurol. 2022 Aug;530(12):2154-2175. doi: 10.1002/cne.25325. Epub 2022 Apr 9.
Olfactory epithelium (OE) is capable of lifelong regeneration due to presence of basal progenitor cells that respond to injury or neuronal loss with increased activity. However, this capability diminishes with advancing age and a decrease in odor perception in older individuals is well established. To characterize changes associated with age in the peripheral olfactory system, an in-depth analysis of the OE and its neuronal projections onto the olfactory bulb (OB) as a function of age was performed. Human olfactory tissue autopsy samples from 36 subjects with an average age of 74.1 years were analyzed. Established cell type-specific antibodies were used to identify OE component cells in whole mucosal sheets and epithelial sections as well as glomeruli and periglomerular structures in OB sections. With age, a reduction in OE area occurs across the mucosa progressing in a posterior-dorsal direction. Deterioration of the olfactory system is accompanied with diminution of neuron-containing OE, mature olfactory sensory neurons (OSNs) and OB innervation. On an individual level, the neuronal density within the epithelium appears to predict synapse density within the OB. The innervation of the OB is uneven with higher density at the ventral half that decreases with age as opposed to stable innervation at the dorsal half. Respiratory metaplasia, submucosal cysts, and neuromata, were commonly identified in aged OE. The finding of respiratory metaplasia and aneuronal epithelium with reduction in global basal cells suggests a progression of stem cell quiescence as an underlying pathophysiology of age-related smell loss in humans. KEY POINTS: A gradual loss of olfactory sensory neurons with age in human olfactory epithelium is also reflected in a reduction in glomeruli within the olfactory bulb. This gradual loss of neurons and synaptic connections with age occurs in a specific, spatially inhomogeneous manner. Decreasing mitotically active olfactory epithelium basal cells may contribute to age-related neuronal decline and smell loss in humans.
嗅上皮（OE）由于存在基底祖细胞而具有终身再生能力，这些祖细胞在受到损伤或神经元丢失时会增加活性。然而，这种能力会随着年龄的增长而减弱，老年人的嗅觉感知能力下降已经得到证实。为了描述与年龄相关的外周嗅觉系统的变化，我们对 OE 及其神经元投射到嗅球（OB）的功能进行了深入分析。对 36 名平均年龄为 74.1 岁的人类嗅觉组织尸检样本进行了分析。使用已建立的细胞类型特异性抗体来识别整个黏膜片和上皮切片中的 OE 成分细胞，以及 OB 切片中的肾小球和肾小球旁结构。随着年龄的增长，嗅上皮面积在整个黏膜上呈向后-背侧方向缩小。嗅觉系统的恶化伴随着含神经元的 OE、成熟的嗅觉感觉神经元（OSN）和 OB 神经支配的减少。在个体水平上，上皮内的神经元密度似乎可以预测 OB 内的突触密度。OB 的神经支配不均匀，腹侧半密度较高，随年龄而降低，而背侧半则保持稳定的神经支配。呼吸性化生、黏膜下囊肿和神经瘤在老年 OE 中很常见。呼吸性化生和神经元上皮的发现以及全球基底细胞的减少表明，作为人类年龄相关性嗅觉丧失的潜在病理生理学，干细胞静止的进展。关键点：人类嗅上皮中嗅觉感觉神经元随年龄的逐渐丧失也反映在嗅球内肾小球的减少。这种随年龄逐渐丧失神经元和突触连接的现象以特定的、空间不均匀的方式发生。嗅上皮有丝分裂活性基底细胞的减少可能导致与年龄相关的神经元衰退和人类嗅觉丧失。
