Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cells’ regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.

中文翻译：

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15-PGDH 在衰老过程中调节造血和胃肠道健康

新出现的证据表明类花生酸分子前列腺素 E2 (PGE2) 在组织损伤后赋予多个器官系统再生表型。由于衰老的部分特征是组织干细胞再生能力的丧失，我们测试了前列腺素降解酶 15-羟基前列腺素脱氢酶 (15-PGDH) 导致老年小鼠器官适应性下降的假设。在这里，我们证明 15-PGDH 的遗传丢失（Hpgd) 对小鼠造血和胃肠 (GI) 组织的衰老具有保护作用。通过外周血细胞计数、骨髓和脾脏干细胞区室评估，缺乏 15-PGDH 的老年小鼠显示出增加的造血输出，并且与 WT 对应物相比，移植后恢复加速。Hpgd表达的缺失还导致胃肠道适应性增强并减少了响应结肠炎的局部炎症。这些结果共同表明，15-PGDH 对衰老组织的再生有负向调节，并且 15-PGDH 抑制可能是改善与年龄相关的器官健康损失的可行治疗策略。