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MLKL deficiency protects against low-grade, sterile inflammation in aged mice.
- Source :
-
Cell death and differentiation [Cell Death Differ] 2023 Apr; Vol. 30 (4), pp. 1059-1071. Date of Electronic Publication: 2023 Feb 08. - Publication Year :
- 2023
-
Abstract
- 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 <superscript>-/-</superscript> and Ripk3 <superscript>-/-</superscript> 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 <superscript>-/-</superscript> 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.<br /> (© 2023. The Author(s).)
Details
- Language :
- English
- ISSN :
- 1476-5403
- Volume :
- 30
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell death and differentiation
- Publication Type :
- Academic Journal
- Accession number :
- 36755069
- Full Text :
- https://doi.org/10.1038/s41418-023-01121-4