Journal Club: Analysis of age-related hearing loss model gene expression data identifies Bsc1l, Aco2 and Ndfs1 as mitochondrial genes with altered expression levels.

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Today's journal article

Ma T, Zeng X, Liu M, Xu S, Wang Y, Wu Q, Zhang T. Analysis and identification of mitochondria-related genes associated with age-related hearing loss. 

Why I picked this article

One of the most prevalent risk factors for developing sensorineural hearing loss is ageing. Our hearing sensitivity in general declines with age, losing hearing to high-frequency sounds first. Just like many other age-related conditions, the development of sensorineural hearing loss with age is thought to be due to the accumulation of oxidative damage caused by reactive oxygen species. Consequently, understanding and targeting reactive oxygen species to prevent the damage has been a key idea for the prevention of hearing loss for a long time. 

Within a given cell, mitochondria are organelles responsible for generating energy; during this process, mitochondria use oxygen and precursors of reactive oxygen species. So healthy mitochondria are very important for regulating oxidative stress and minimising damage to the cell. Mitochondria are fascinating organelles with their own DNA, called mitochondrial DNA, which contains many genes, some of which are associated with diseases (http://www.mitomap.org). 

In this study, the authors have used a bioinformatics approach to investigate mitochondrial genes associated with age-related sensorineural hearing loss. 

Some of the research findings

Database data & analysis: 
Validation work:
  • HEI-OC1 cell line purchased from Ubigene Company was used. This is an immortalised cell line derived from the mouse inner ear. 
  • HEI-OC1 cells were treated with 30 mg/ml D-galactose for 72 hours to simulate senescent hair cells. Gene expression change in these cells were studied. 
Finding:
  • 503 genes were upregulated in the age-related sensorineural hearing loss model. 
  • 233 genes were upregulated, or increased, in the age-related sensorineural hearing loss model. 
  • A total of 28 mitochondrial genes were identified that had altered expression in the age-related sensorineural hearing loss group. 
  • 10 key genes identified were: Arg2, Fdx1, Aco2, Nduls1, Ndufaf5, Bcs1l, Nsun2, Sdhaf1, Mtif2, Mrpl24. 
  • In D-galactose treated HEI-OC1 cells, the expression of three key genes, BSC1L, ACO2 and NDFS1 all decreased. 
Figure 4B. 10 mitochondrial genes of significant change in the age-related hearing loss in mice. Ma et al. 2025

Haruna's takeaway

This study identified that some genes may be particularly changed in the model of age-related hearing loss. What that means is still to be investigated. For our notes, what we know about the three genes these authors identified through database analysis were: 
  • BSC1L; an important protein that makes up the complex III of the mitochondria electron transport chain.
  • ACO2; an enzyme that is part of the Krebs cycle.
  • NDFS1; a constituent of complex I. 

I think what is interesting perhaps, is that some mitochondrial genes are upregulated in age-related hearing loss in particular, instead of all mitochondrial genes changing equally? There may be some vulnerability in certain parts of the mitochondria or the metabolic pathways related to ageing. 

An interesting point was actually the analysis parts; there were many tools used in these research publications to re-analyse the open-access data in the database. This is useful and good for science. The more we can share and use data in the public database, the more we can get out of limited scientific data and experiments. 

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This is Haruna's 68/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.