Tumor necrosis factor-alpha mediated inflammation versus apoptosis in age-related hearing loss

An almost universal phenomenon occurring during aging is a state of chronic, low-grade, sterile inflammation. Inflammation is a crucial contributor to various age-related pathologies and natural processes in aging tissues. Tumor necrosis factor-alpha (TNF-alpha), a master regulator of the immune system, plays an important role in the propagation of inflammation. Recent research has found correlations between hearing loss and markers such as TNF-alpha. However, the intrinsic molecular mechanism by which TNF-alpha influences aging individuals' increased risk of hearing loss remains unclear. In this study, we found that TNF-alpha expression gradually increased with age in DBA/2J mice. We then used recombinant TNF-alpha to upregulate TNF-alpha levels in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and found that low concentrations of TNF-alpha could activate the nuclear factor kappa B (NF-kappa B) transcriptional response to mediate hair cell survival, while high concentrations of TNF-alpha could activate the Caspase-3 cascade to mediate hair cell apoptosis, which preliminarily confirmed that a TNF-alpha mediated signaling pathway plays an important role in the pathogenesis of age-related hearing loss.