2023-09-03 06:08:56
Researchers have found that age-related hearing loss is linked to lower cholesterol in the inner ear. Their experiments revealed that phytosterol supplements can replace lost cholesterol and prevent sensory dysfunction in mice.
María Eugenia Gomez-Casati and her team from the Institute of Pharmacology, School of Medicine, University of Buenos Aires-CONICET, alongside Mauricio Martin from the Mercedes Medical Research Institute, and Martín Ferreyra from INIMEC-CONICET- UNC, National University of Cordoba in Argentina, discovered a link between age-related hearing loss and lower cholesterol levels in the inner ear.
Their experiences, recently published in the journal Biology PLOSshow that phytosterol supplements were able to act in place of lost cholesterol and prevent sensory dysfunction in mice.
Sensory cells in the inner ear called outer hair cells (OHCs) amplify sounds by changing their length. As we age, these cells lose their ability to stretch in response to sound, preventing sound amplification and leading to age-related hearing loss. Since cholesterol plays a key role in the stretch response and brain cholesterol has recently been shown to decrease with age, researchers hypothesize that hearing loss may be related to loss of cholesterol in COHs. This hypothesis was tested in mice.
First, the researchers measured the amount of CYP46A1 in OHCs in the inner ear, as this enzyme helps break down and recycle cholesterol. As expected, they found more CYP46A1 in the inner ears of older mice than in younger mice, and therefore less cholesterol. Next, they showed a causal link by inducing hearing loss in young mice, as indicated by abnormal production of inner ear cells, by overactivating CYP46A1 with a drug.
Expression of prestin in OHCs from control, efavirenz, and efavirenz plus phytosterol-treated mice. Credit: Sodero AO et al., 2023, PLOS Biology, CC-BY 4.0
Finally, they tested whether raising cholesterol in the brain might counteract the drug. Since cholesterol itself cannot enter the brain from the blood, the researchers used cholesterol-like plant compounds called phytosterols that can. Young mice that received both the CYP46A1-activating drug and 3 weeks of dietary phytosterols showed improved OHC function.
Since phytosterols can be found in many over-the-counter supplements, they might be a handy way to combat age-related hearing loss. However, it will be necessary to directly test their effects on hearing loss in older mouse models as well as in humans before more definitive conclusions can be drawn.
The authors add: “In the present work, we show that: 1) aging triggers cholesterol loss in sensory cells of the inner ear, 2) a widely used retroviral treatment for HIV/AIDS patients reproduces the cholesterol loss seen in older individuals, and leads to impaired outer hair cell function and 3) we have found that these defects can be partially reversed by phytosterol supplementation. Our results are very promising as they provide the first proof of principle supporting phytosterol supplementation as a possible approach for the prevention or treatment of hearing loss.
This research was funded by Agencia Nacional de Promoción Científica y Técnica (Argentina) grant PICT-2018-00539 to MEGC and grant PICT-2018-00648 to MGMAOS received financial support from Pontificia Universidad Católica Argentina. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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