IGF-1 and SLC25A33 preserve cochlear blood barrier integrity in aged mice
Targeting this pathway curbs mitochondrial oxidative stress and pericyte activation to partially restore auditory function in mouse models.
Aging cell · Xu R et al. · Paper published 30 Sep 2026
Researchers analyzed gene expression in inner ear pericytes from young and aged mice. They observed significant downregulation of Igf1 and Slc25a33 in aged pericytes alongside elevated TGF-beta signaling. In mouse cell cultures, IGF-1 deficiency reduced SLC25A33 expression, generated mitochondrial reactive oxygen species, and activated TGF-beta/Smad2 signaling. This drove pericyte phenotypic switching marked by increased alpha-SMA and reduced E-cadherin. In living mice, suppressing either IGF-1 or SLC25A33 damaged the ultrastructure of the blood-labyrinth barrier and exacerbated hearing loss. In contrast, delivering exogenous IGF-1 or overexpressing SLC25A33 suppressed these pathological shifts and partially restored auditory function.
Why it matters
The findings define a molecular mechanism connecting vascular barrier integrity and mitochondrial stress to age-related sensory decline. This identifies specific signaling targets that could inform future strategies to treat age-related hearing loss.
Caveats
The study was conducted exclusively in mice and cell culture systems, meaning the therapeutic relevance to human hearing loss remains to be tested.
Written from the paper’s abstract, and every claim checked against it before publishing. Read the paper for the full methods and data.
The paper
IGF-1/SLC25A33 Maintains Blood-Labyrinth Barrier Integrity by Suppressing TGF-β/Smad2-Mediated Pericyte Activation in Age-Related Hearing Loss
Xu R, Tang J, Lin H et al.
Aging cell · 30 Sep 2026 · Peer-reviewed
- Relevance
- Core geroscience
- News value
- Notable
- Evidence
- Animals
- Status
- Peer-reviewed
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