Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength
Adelaida R. Palla, Meenakshi Ravichandran, Yu Xin Wang, L. А. Alexandrova, Ann V. Yang, Peggy E. Kraft, Colin Holbrook, Christian M. Schürch, Andrew Tri Van Ho, Helen M. Blau
Abstract
Maintaining muscle Prostaglandin E2 (PGE2), an eicosanoid that mediates inflammatory responses, also supports the function of muscle stem cells. Palla et al. found that loss of PGE2 in aging mice contributes to loss of muscle and appears to be a consequence of increased activity of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme that degrades PGE2 (see the Perspective by Becker and Rudolph). Restoring PGE2 concentrations by inhibiting 15-PGDH in older mice improved muscle function. Decreased activity of 15-PGDH in older animals had beneficial effects that included decreased proteolysis and transforming growth factor–β signaling and increased mitochondrial function and autophagy. The findings reveal a potential therapeutic strategy to help maintain muscle mass and function during aging. Science , this issue p. eabc8059 ; see also p. 462