Li Dianrong, Meng Lingjun, Xu Tao, Su Yaning, Liu Xiao, Zhang Zhiyuan, Wang Xiaodong
National Institute of Biological Sciences, Beijing, China.
Elife. 2017 Aug 15;6:e27692. doi: 10.7554/eLife.27692.
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 3- and -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.
一对激酶RIPK1和RIPK3以及RIPK3底物MLKL在哺乳动物中引发一种程序性坏死性细胞死亡形式，称为坏死性凋亡。我们在此报告，3 -敲除和 -敲除小鼠的雄性生殖器官在高龄时仍保持“年轻”的形态和功能，而年龄匹配的野生型小鼠的生殖器官则会退化。在老年野生型小鼠睾丸的精原干细胞中可检测到坏死性凋亡的激活标志物MLKL的RIPK3磷酸化，但在年轻小鼠中未检测到。当给年轻野生型小鼠的睾丸施加局部坏死性凋亡刺激时，其生殖器官显示出加速衰老。在野生型小鼠生殖器官正常出现与年龄相关变化之前，用RIPK1抑制剂喂养可阻止衰老迹象的出现。因此，睾丸中的坏死性凋亡促进了小鼠雄性生殖系统与衰老相关的退化。
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