Dietary supplementation with phytosterols — plant sterols with structure and function similar to cholesterol — prevented sensory dysfunction in lab mice.
Representative confocal images of whole mounts organ of Corti from the medial region of the cochlea stained for filipin to label cholesterol (green) and phalloidin for visualizing actin in stereocilia (blue) from young (top) and old (bottom) C57BL/J mice. Scale bar – 30 μm. Rectangles indicate the region of the zoomed-in areas shown on the right using a 63x objective. Scale bar – 8 μm. Pink dotted lines represent the diameter of individual inner hair cells and outer hair cells. Image credit: Sodero et al., doi: 10.1371/journal.pbio.3002257.
“Functional deterioration of the nervous system is frequently observed in the elderly, with a progressive decline in cognitive capacities,” said Dr. María Eugenia Gomez-Casati, a researcher at the Universidad de Buenos Aires and CONICET, and her colleagues.
“Age-related hearing loss is a significant problem that leads to a reduced hearing perception, with almost 1 in 3 adults over age 65 experiencing some degree of hearing loss.”
“Age-related hearing loss typically initiates with a loss of synaptic connections between inner hair cells and auditory nerve fibers and a loss of outer hair cells in the high-frequency region of the cochlea. Nonetheless, the cellular and molecular mechanisms underlying these age-related losses remain mostly unknown.”
“Outer hair cells are sensory cells implicated in the mechanical amplification of sounds and in the frequency selectivity in mammals,” they said.
“Outer hair cells respond to changes in membrane voltage with changes in length, a phenomenon known as electromotility, which is brought about by the motor protein prestin, a polytopic integral membrane protein present in the outer hair cell’s lateral wall.”
“The organization of the outer hair cell lateral wall is exclusive among hair cells and other mammalian cell types because it contains a tightly regulated level of cholesterol.”
“It has been postulated that alterations in the cholesterol content in the lateral wall might modulate the function and/or distribution of prestin within the plasma membrane.”
“We hypothesize that cholesterol deficiency might play a role in the associated cochlear pathologies that occur during aging. However, the role of cholesterol homeostasis in the physiopathology of the inner ear has not been studied.”
In the study, the researchers measured the levels of the cholesterol 24-hydroxylase (CYP46A1) — the main enzyme responsible for cholesterol turnover in the brain — and cholesterol content in the inner ear of young and aged mice.
As expected, they found more CYP46A1 in the inner ears of older mice than in younger mice, and consequently less cholesterol.
Next, they showed cause and effect by inducing hearing loss in young mice, as indicated by abnormal inner ear-cell output, by over-activating CYP46A1 with a drug.
Finally, they tested whether increasing cholesterol in the brain could counter the drug.
Since cholesterol itself cannot actually enter the brain from the blood, the researchers used plant-based cholesterol-like compounds called phytosterols which can.
The young mice who got both the CYP46A1-activating drug and 3 weeks of dietary phytosterols displayed improved outer hair cell function.
As phytosterols can be found in many over-the-counter supplements, they could be a convenient way to combat age-related hearing loss.
However, directly testing their effects on hearing loss in older mouse models as well as in humans will be necessary before more definite conclusions can be made.
“In the present work we show that aging triggers cholesterol loss from sensory cells of the inner ear; that a retroviral treatment widely employed for HIV/AIDS patients reproduces the cholesterol loss observed in aged individuals and leads to impaired outer hair cells’ function; and that these defects can be partly reversed by phytosterols supplementation,” the scientists said.
“Our findings are very promising because they provide the first proof-of-principle supporting phytosterols supplementation as a possible approach for prevention or treatment of hearing loss.”
The study was published online in the journal PLoS Biology.
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A.O. Sodero et al. 2023. Phytosterols reverse antiretroviral-induced hearing loss, with potential implications for cochlear aging. PLoS Biol 21 (8): e3002257; doi: 10.1371/journal.pbio.3002257
