RIPK1-RIPK3-MLKL-dependent necrosis promotes the aging of mouse male reproductive system.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 28807105.
- Also identified by DOI 10.7554/eLife.27692 and PMC identifier 5557593.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
A pair of kinases, RIPK1 and RIPK3, as well as the RIPK3 substrate MLKL cause a form of programmed necrotic cell death in mammals termed necroptosis. We report here that male reproductive organs of both <i>Ripk</i>3- and <i>Mlkl</i>-knockout mice retain 'youthful' morphology and function into advanced age, while those of age-matched wild-type mice deteriorate. The RIPK3 phosphorylation of MLKL, the activation marker of necroptosis, is detected in spermatogonial stem cells in the testes of old but not in young wild-type mice. When the testes of young wild-type mice are given a local necroptotic stimulus, their reproductive organs showed accelerated aging. Feeding of wild-type mice with an RIPK1 inhibitor prior to the normal onset of age-related changes in their reproductive organs blocked the appearance of signs of aging. Thus, necroptosis in testes promotes the aging-associated deterioration of the male reproductive system in mice.
Medical subject headings
- Aging
- Genitalia, Male
- Necrosis
- Protein Kinases
- Receptor-Interacting Protein Serine-Threonine Kinases