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

Autor: Palla AR; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Ravichandran M; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Wang YX; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Alexandrova L; Vincent Coates Foundation Mass Spectrometry Laboratory, Stanford University, Stanford, CA, USA., Yang AV; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Kraft P; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Holbrook CA; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Schürch CM; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.; Nolan Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA., Ho ATV; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA., Blau HM; Blau Laboratory, Stanford School of Medicine, Stanford, CA 94305, USA. hblau@stanford.edu.; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford, CA 94305, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2021 Jan 29; Vol. 371 (6528). Date of Electronic Publication: 2020 Dec 10.
DOI: 10.1126/science.abc8059
Abstrakt: 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 E 2 (PGE 2 )-degrading enzyme, as a hallmark of aged tissues, including skeletal muscle. The consequent reduction in PGE 2 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 PGE 2 concentrations, which augmented mitochondrial function and autophagy and decreased transforming growth factor-β signaling and activity of ubiquitin-proteasome pathways. Thus, PGE 2 signaling ameliorates muscle atrophy and rejuvenates muscle function, and 15-PGDH may be a suitable therapeutic target for countering sarcopenia.
(Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
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