Researchers have found that age-related hearing loss is associated with a decrease in cholesterol in the inner ear. Their experiments revealed that phytosterol supplements could replace lost cholesterol and prevent sensory dysfunction in mice.
Maria Eugenia Gómez Casati and her team from the Institute of Pharmacology, CONICET Medical School, University of Buenos Aires, Mauricio Martin from the Mercedes Institute of Medical Research, and Martin Ferreira from INIMEC-CONICET-UNC, National University of Cordoba Argentinian researchers found an association between age-related hearing loss and lower cholesterol levels in the inner ear.
Their experiment recently published in a magazine PLOS biologyshow that phytosterol supplementation can replace lost cholesterol and prevent sensory dysfunction in mice.
Sensory cells in the inner ear called outer hair cells (OHCs) amplify sound by varying their length. As we age, these cells lose their ability to stretch in response to sound, impeding sound amplification and leading to age-related hearing loss. Cholesterol plays a key role in the stretch response, and it has recently been shown that brain cholesterol declines with age, so researchers suspect that hearing loss may be related to the decline in OHC cholesterol. made the hypothesis. This hypothesis was tested in mice.
First, the researchers measured the amount of CYP46A1 in inner ear OHCs. Because this enzyme helps break down and recycle cholesterol. As expected, older mice were found to have more CYP46A1 and consequently less cholesterol in the inner ear than younger mice. We next showed that drug overactivation of CYP46A1 was causal by inducing hearing loss in young mice, as indicated by abnormalities in inner ear cell output.
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Prestin expression in OHCs of control, efavirenz, and efavirenz and phytosterol-treated mice. Credit: Sodero AO et al., 2023, PLOS Biology, CC-BY 4.0
Finally, they tested whether drugs could be counteracted by increasing cholesterol in the brain. Cholesterol itself cannot actually enter the brain from the blood, so the researchers used plant-derived cholesterol-like compounds called phytosterols that can uptake cholesterol. Young mice receiving both CYP46A1 activators and 3 weeks of dietary phytosterols showed improved OHC function.
Phytosterols are found in many over-the-counter supplements and can be a convenient way to combat age-related hearing loss. However, it would be necessary to directly test the effects on hearing loss in older mouse models as well as in humans before making more definitive conclusions.
The authors further stated, “In this study, we found that 1) aging causes cholesterol loss from sensory cells in the inner ear, and 2) retroviral therapy, which is widely used in HIV/AIDS patients, reduces 3) found that these deficiencies could be partially reversed by phytosterol supplementation.Our findings suggest that phytosterol supplementation as a possible approach for the prevention or treatment of hearing loss. It is very promising as it provides a first proof of principle in favor of
Reference: “Phytosterols reverse antiretroviral-induced hearing loss and have potential effects on cochlear aging,” Alejandro O. Sodero, Valeria C. Castagna, Setienbre D. Errolza, Sarah M. By Gonzalez Rodulfo, Maria A. Paulazo, and Jimena A. Ballestero, Mauricio G. Martin and Maria Eugenia Gomez-Cassati, 24 Aug. 2023, PLOS biology.
DOI: 10.1371/journal.pbio.3002257
This work was supported by a PICT-2018-00539 grant to the Agencia Nacional de Promoción Centífica y Técnica (Argentina) MEGC and a PICT-2018-00648 grant to the MGMAOS and received financial support from the Argentine Pontifical Universidad Católica. . Funders had no role in study design, data collection and analysis, publication decisions, or manuscript preparation.