Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength

Treatments are lacking for sarcopenia, a debilitating age-related skeletal muscle wasting syndrome. We identifed increased amounts of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the prostaglandin E2 (PGE2)–degrading enzyme, as a hallmark of aged tissues, including skeletal muscle. The consequent reduction in PGE2 signaling contributed to muscle atrophy in aged mice and results from 15-PGDH–expressing myofibers and interstitial cells, such as macrophages, within muscle. Overexpression of 15-PGDH in young muscles induced atrophy. Inhibition of 15-PGDH, by targeted genetic depletion or a small-molecule inhibitor, increased aged muscle mass, strength, and exercise performance. These benefits arise from a physiological increase in PGE2 concentrations, which augmented mitochondrial function and autophagy and decreased transforming growth factor–β signaling and activity of ubiquitin-proteasome pathways. Thus, PGE2 signaling ameliorates muscle atrophy and rejuvenates muscle function, and 15-PGDH may be a suitable therapeutic target for countering sarcopenia.

Source: ScienceNOW - January 28, 2021 Category: Science Authors: Palla, A. R., Ravichandran, M., Wang, Y. X., Alexandrova, L., Yang, A. V., Kraft, P., Holbrook, C. A., Schürch, C. M., Ho, A. T. V., Blau, H. M. Tags: Cell Biology, Medicine, Diseases, Online Only r-articles Source Type: news