| First Author | Tovey Crutchfield EC | Year | 2023 |
| Journal | Cell Death Differ | Volume | 30 |
| Issue | 4 | Pages | 1059-1071 |
| PubMed ID | 36755069 | Mgi Jnum | J:353304 |
| Mgi Id | MGI:7461002 | Doi | 10.1038/s41418-023-01121-4 |
| Citation | Tovey Crutchfield EC, et al. (2023) MLKL deficiency protects against low-grade, sterile inflammation in aged mice. Cell Death Differ 30(4):1059-1071 |
| abstractText | MLKL and RIPK3 are the core signaling proteins of the inflammatory cell death pathway, necroptosis, which is a known mediator and modifier of human disease. Necroptosis has been implicated in the progression of disease in almost every physiological system and recent reports suggest a role for necroptosis in aging. Here, we present the first comprehensive analysis of age-related histopathological and immunological phenotypes in a cohort of Mlkl(-/-) and Ripk3(-/-) mice on a congenic C57BL/6 J genetic background. We show that genetic deletion of Mlkl in female mice interrupts immune system aging, specifically delaying the age-related reduction of circulating lymphocytes. -Seventeen-month-old Mlkl(-/-) female mice were also protected against age-related chronic sterile inflammation in connective tissue and skeletal muscle relative to wild-type littermate controls, exhibiting a reduced number of immune cell infiltrates in these sites and fewer regenerating myocytes. These observations implicate MLKL in age-related sterile inflammation, suggesting a possible application for long-term anti-necroptotic therapy in humans. |
