Correspondence. Localised degeneration occurs in aged mouse olfactory epithelium

Abstract

Olfactory neuroepithelium of adult vertebrates retains a population of basal stem cells capable, throughout life, of dividing and differentiating into mature olfactory receptor neurons (see Farbman, 1994). The rate of turnover of olfactory receptor neurons is influenced, in part, by environmental conditions (Hinds et al. 1984). The olfactory system is known, however, to undergo a general decline in function with age. Age‐related changes have been described in the rat olfactory bulb, with a decline in size in later life (Hinds & McNelly, 1981). However, this was thought to be secondary to changes within the olfactory epithelium as changes in the number of olfactory receptor neurons directly influence the size of the olfactory bulb. Thus the primary deficit in declining olfactory function may reside in the olfactory epithelium. Studies in humans demonstrated that olfactory function diminishes with increasing age (Ship et al. 1996), suggesting a possible decrease in the number of olfactory sensory neurons. Although the structure of both developing and mature olfactory epithelium (Farbman, 1994) have been well characterised, less information exists on changes relating specifically to ageing. A reduction in thickness of the olfactory epithelium was evident in ageing humans, with a concomitant loss of the normal zonal distribution of supporting and sensory cell nuclei, a less well defined boundary between respiratory and sensory epithelia, and an increase in pigment granules within the supporting cells (Naessen, 1971). Similar lysosome‐like inclusion bodies were also noted in olfactory epithelium of adult rabbits (Mulvaney, 1971) and dogs over the age of 17 y (Hirai et al. 1996). Decreases both in the total area of olfactory epithelium and in dendritic knob density have been described in rats aged 29 mo and above (Hinds & McNelly, 1981). This is unlikely to be due to a loss of regenerative capacity since, in hamsters, regeneration of olfactory receptor neurons is observed in aged animals (Morrison & Costanzo, 1995). A scanning electron microscopic comparison of young and old rat olfactory epithelium revealed changes in membrane‐limited dense bodies in olfactory receptor neuronal cell bodies (Naguro & Iwashita, 1992). In old rats (21 and 36 mo), large irregular bodies were found in the supranuclear area of olfactory receptor neurons and were also abundant throughout the sustentacular cells, resulting in cell enlargement and the loss of about 2 layers of olfactory receptor neuron perikarya. They contained lipid droplets and numerous irregular osmiophilic lamellae resembling lipofuscin granules (Naguro & Iwashita, 1992). No attempt was made to quantify these age related changes. The present study aimed to detail fully the morphological changes in the aged mouse olfactory epithelium and is a continuation of a previous pilot study (Appleton et al. 1996).

Distinct Types of Lipofuscin Pigment in the Hippocampus and Cerebellum of Aged Cheirogaleid Primates

“…It is interesting to notice that the presence of numerous small lipid droplets seemed to be characteristic of dentate gyrus cells. In general, lipofuscin granules display the same physical and biochemical characteristics at some stage of their evolution (Harman, ) and the electron dense fraction of the granules increases with age (Breckenridge et al, ; Siakotos et al, ). Large aggregates of lipofuscin granules with few vacuoles are observed in the more advanced stages of cell atrophy (Nixon et al, ).…”

Olfactory Epithelium Grafts in the Cerebral Cortex: An Immunohistochemical Analysis

“…Olfactory epithelium in the normal adult human tends to regress and become replaced by respiratory epithelium, 15–17 and in aged mice there is thinning of epithelium with a decreased number of olfactory dendrite knobs. 18 Often, olfactory epithelium lesioned with chemicals is only partially replaced with neuroepithelium and the remainder is replaced with respiratory‐type epithelium. 19 Human olfactory epithelium biopsy specimens from viral‐induced anosmic patients have shown absence of olfactory receptor cells with an increase in supporting and basal cells.…”

Anosmia: an evolution of our understanding of its importance in COVID-19 and what questions remain to be answered

“…Older patients are at higher risk of more severe disease; of course olfactory function diminishes with increasing age [28] and, therefore, hospitalized patients may simply have higher rates of pre-existing loss, and may be less able to detect further decline. Brekenridge and colleagues have described age-related loss of sustentacular cell nuclei as well as olfactory receptor neuron nuclei in animal models [29]. Knowing that sustentacular cells of the neuroepithelium are those which express the most ACE-2, the gateway to SARS-CoV2, one could imagine that the degenerative impairment linked to the age of these cells could explain the less significant incidence anosmia in elderly patients with a severe form of COVID-19 infection.…”