Function (biology)

Cell biology

Biology

Catabolism

Eicosanoid

Proteolysis

Arachidonic acid

Muscle mass

Endocrinology

Apoptosis

Autophagy

Biochemistry

Skeletal muscle

Sarcopenia

Prostaglandin E2

Prostaglandin

Enzyme

Myocyte

Dehydrogenase

Internal medicine

Mitochondrion

Medicine

Chemistry

Science

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.

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