# Pyroptosis

Pyroptosis is a highly inflammatory form of programmed cell death. The executioners are 'gasdermin' proteins, especially gasdermin D (GSDMD). Inflammatory caspases cut GSDMD. (In humans these are caspase-1, -4, and -5; in mice, caspase-11.) Once cut, GSDMD clusters and punches pores in your cell's membrane. There are two paths. In the canonical path, caspase-1 cuts GSDMD and also matures IL-1β and IL-18 for release. In the non-canonical path, caspase-4/-5/-11 cut GSDMD to form pores. Then IL-1β and IL-18 maturation needs a second step (NLRP3 and caspase-1, triggered by potassium leaving through the pores). Pyroptosis fires downstream of inflammasome complexes, like the NLRP3 inflammasome. The triggers are germ signals, damage signals, and sterile stress. In aging and age-related disease, dysregulated pyroptosis fuels tissue inflammation. That shows up in atherosclerosis, neurodegeneration, and metabolic disease.

## Sources

- Shi J, Gao W, Shao F. (2017). Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends in Biochemical Sciences. https://doi.org/10.1016/j.tibs.2016.10.004
- Shi J, Zhao Y, Wang K, et al.. (2015). Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. https://doi.org/10.1038/nature15514

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_Canonical: https://longevity-switzerland.com/en/glossary/pyroptosis · Part of Longevity Cities · Updated 2026-06-22_