The Seminar is held each Tuesday during the semester from noon-1 p.m.
Title: Epigenetic erosion of H4K20me1 induced by inflammation drives aged stem cell ferroptosis
Abstract: Aging is typically characterized by a decline in the functionality and number of stem cells across the organism. In this study, we uncovered a novel mechanism by which systemic inflammation drives muscle stem cell (MuSC) aging through erosion of H4K20me1, an epigenetic mark crucial for maintaining MuSC quiescence. We demonstrated that age-related inflammation decreases the levels of H4K20me1 in MuSCs, disrupting their quiescence and inducing ferroptosis, a form of iron-dependent cell death. Our findings show that inflammatory signals downregulate Kmt5a, the enzyme responsible for depositing H4K20me1, leading to the epigenetic silencing of anti-ferroptosis genes. This results in aberrant iron metabolism, increased reactive oxygen species levels, and lipid peroxidation in aged MuSCs. Importantly, long-term inhibition of systemic inflammation initiated at 12 months of age effectively prevents ferroptosis, preserves MuSC numbers, and enhances muscle regeneration, ultimately extending the lifespan of mice. These findings revealed an epigenetic switch that links chronic inflammation to MuSC aging and ferroptosis, offering potential therapeutic strategies for combatting age-related muscle degeneration.
This event is offered in a hybrid format:
- The in-person seminar is being held at the Discovery Building, DeLuca Forum.
- To join online, please click the zoom link below:
- https://uwmadison.zoom.us/j/96958883460
- *if you are asked for a passcode: 970506
- https://uwmadison.zoom.us/j/96958883460