15-PGDH regulates hematopoietic and gastrointestinal fitness during aging

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.

Automated summary

Emerging evidence suggests that prostaglandin E2 (PGE2), an eicosanoid molecule, plays an important role in promoting tissue regeneration in multiple organ systems after injury. As aging is characterized by a decline in the regenerative capacity of tissue stem cells, this study investigated the role of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the diminished organ fitness of aged mice. The results showed that genetic loss of 15-PGDH conferred a protective effect on the aging of murine hematopoietic and gastrointestinal tissues. Aged mice lacking 15-PGDH showed increased hematopoietic output and accelerated recovery after transplantation compared to their wild-type counterparts. Additionally, loss of Hpgd expression resulted in improved gastrointestinal fitness and reduced inflammation in response to colitis. These findings suggest that 15-PGDH negatively regulates tissue regeneration in aging and that inhibiting 15-PGDH could be a potential therapeutic strategy to alleviate age-related loss of organ fitness.