Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc degeneration, and osteoarthritis.
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-α (TNF-α), 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-α. However, the intrinsic molecular mechanism by which TNF-α influences aging individuals’ increased risk of hearing loss remains unclear. In this study, we found that TNF-α expression gradually increased with age in DBA/2J mice. We then used recombinant TNF-α to upregulate TNF-α levels in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and found that low concentrations of TNF-α could activate the nuclear factor kappa B (NF-κB) transcriptional response to mediate hair cell survival, while high concentrations of TNF-α could activate the Caspase-3 cascade to mediate hair cell apoptosis, which preliminarily confirmed that a TNF-α mediated signaling pathway plays an important role in the pathogenesis of age-related hearing loss.
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