Environmental enrichment modulates silent information regulator 1 (SIRT1) activity to attenuate central presbycusis in a rat model of normal aging.

Age-related hearing loss (ARHL) is sensory impairment in the elderly. This study aimed to identify a critical molecular mechanism that can maintain young phenotypes. We focused on the effect of exposure to environmental enrichment (EE) for 12 weeks in the central auditory pathway and limbic system of aged rats. The effects of EE were compared with the effects of dexamethasone administration. We found that in 74-week-old rats hearing function was significantly reduced and the number of neuronal specific nuclear protein (NeuN)-positive cells was decreased by 10-15% in the auditory cortex, amygdala, and hippocampus. EE exposure did not significantly affect the number of neurons, but DX administration significantly decreased their numbers in the amygdala compared with untreated aged rats. Both treatments reduced inducible nitric oxide synthase (iNOS) expression in the auditory pathway and limbic system. Exposure to EE significantly increased silent information regulator 1 (SIRT1) expression and activity, and nicotinamide phosphoribosyltransferase (NAMPT) concentration. In this study, the exposure to EE resulted in attenuated age-related hearing loss accompanied by reduction of iNOS expression and increase SIRT1 activity and NAMPT level. These data showed that EE may be a potential therapeutic to prevent ARHL.

• Publication year

  2021

• Venue

  Experimental Gerontology

• Publication date

  2021-09-13

• Fields of study

  Medicine, Environmental Science

• Identifiers
  DOI 10.1016/j.exger.2021.111552PMID 34530105
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Chronic inflammation - inflammaging - in the ageing cochlea: A novel target for future presbycusis therapy.

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  2015cited by this paper
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  2011cited by this paper
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