Journal Club: Comprehensive mapping of age-related signatures in female CBA/CaJ mouse (2-3 month old versus 2-3 year-old)

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Today's journal article

Inuzuka Y, Mizutari K, Kurioka T, Suzuki J, Koizumi Y, Araki K, Shiotani A. Histopathological change of age-related hearing loss in female advance-aged CBA/CaJ mice. 

Why I picked this article

Ageing is a big risk factor for sensorineural hearing loss. In humans, with ageing, we slowly and progressively lose high-frequency hearing. We currently do not have any means to stop or slow down the age-related changes to the inner ear. 

Some strains of mice commonly used for biomedical research (e.g. C57BL/J mice) develop hearing loss at a young age due to the genetic background of the sub-strain. In these animals, studying the true effect of "ageing" can be difficult. CBA/CaJ mice are a standard model for studying age‑related hearing loss because they retain good hearing into mid‑life and decline later. This is similar to what we perceive as hearing loss in human ageing. 

This research follows very old female CBA/CaJ mice and quantifies changes across the whole cochlea between young and old animals. These include the hearing function, sensory hair cell counts, synapses between sensory and neural cells, and homeostasis in the cochlear and auditory nerve fibres. This establishes a good baseline that we can refer to as we compare different animal models, particularly mouse models. 

Some of the research findings

Animal Models: 
  • Strain and sex: female CBA/CaJ mice.
  • Advanced‑aged group: 129–138 weeks (about 2.5–2.7 years; n = 11 mice)
  • Young age group: 9–14 weeks (n = 12 mice).
  • Ears included for histology and physiology as specified per assay. 
  • The ambient noise in the environment animals were in: 
    • The background noise had a biomodal frequency distribution with peaks at 315 and 1000 Hz. 
    • The average LZeq, LZFmax, and LZFmin at the rearing shelf of mice are 76.7, 82.0, and 71.5dB SPL
Key finding: 
  • Auditory brainstem response (ABR): hearing thresholds were significantly higher at all test frequencies in aged mice: 
    • Effect sizes were very large (e.g., Cohen d ≈ 10.2 at 5.6 kHz; 12.6 at 16 kHz). 
    • Wave I (P1) amplitudes were reduced and latencies prolonged at 80 dB SPL in aged mice.
  • Distortion‑product otoacoustic emissions (DPOAE): thresholds were elevated in aged mice between 11.30-32kHz, consistent with outer hair cell dysfunction.
  • Hair cell number for both inner and outer hair cells were decreased. 
    • outer hair cells were markedly reduced across turns, down to ~25% of young mice in lower frequency zones and 50% in higher frequency area. 
    • Inner hair cells showed a smaller but significant loss, down to 75% of young mice at the lowest number observed at 16kHz. 
  • Synapses were counted and normalised per inner hair cells of young animal. 
    • Paired CtBP2/GluA2 counts showed reduced coupled synapses and more orphan ribbons in aged mice (50-80% of young animal hair cell) 
    • The strongest effects at mid to high frequencies.
  • Stria vascularis and endolymph were also changed.
    • Stria vascularis area were significantly decreased to 55-60% of young animal. 
    • Stria vascularis (SV): semithin sections and TEM showed SV atrophy, narrowed/distorted capillaries with endothelial hypertrophy, and degenerating intermediate cells adhering to marginal cells. Pigmented macrophages were prominent.
  • SGNs: survival was about 60% on average in aged cochleae, with TEM evidence of cellular senescence (lipofuscin granules, vacuolation, segmented nucleoli) and fewer mitochondria per soma.
  • Plasma d‑ROMs (hydroperoxides) were higher in aged mice (mean ~204 vs ~115 CARR units), supporting a systemic oxidative shift that aligns with cochlear mitochondrial changes.
From part of Fig8A. Auditory nerve fibre in the osseus spiral lamina in young (top) and aged (bottom) animals. Inuzuka et al. 2025

Haruna's takeaway

This is such a comprehensive research study, covering various elements within the cochlea. The electron microscopy investigation of auditory nerve changes is very nice and beautiful. While very fundamental, the comprehensive baseline data like this is very useful as a reference guide. 

Animal models with certain backgrounds are not available consistently across the globe. For example, we do not have access to CBA/CaJ mice at the University of Auckland, currently. The environment in which animals are, such as nutrition and ambient noise level, is likely to differ between different institutions. Those things may add up to some inconsistency in basic science, and the impact may be most relevant to something like ageing-related pathology due to the long time needed to slowly develop the pathology. 

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This is Haruna's 92/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.