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Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength
A R Palla 1 2, M Ravichandran 1 2, Y X Wang 1 2, L Alexandrova 3, A V Yang 1 2, P Kraft 1 2, C A Holbrook 1 2, C M Schürch 2 4, A T V Ho 1 2, H M Blau 5 2
Abstract:
...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.
PMID: 33303683
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938328/
