RT Journal Article
SR Electronic
T1 Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength
JF Science
JO Science
FD American Association for the Advancement of Science
SP eabc8059
DO 10.1126/science.abc8059
A1 Palla, A. R.
A1 Ravichandran, M.
A1 Wang, Y. X.
A1 Alexandrova, L.
A1 Yang, A. V.
A1 Kraft, P.
A1 Holbrook, C. A.
A1 Schürch, C. M.
A1 Ho, A. T. V.
A1 Blau, H. M.
YR 2020
UL http://science.sciencemag.org/content/early/2020/12/09/science.abc8059.abstract
AB Treatments are lacking for sarcopenia, a debilitating age-related skeletal muscle wasting syndrome. Here we identify elevated 15-PGDH, the Prostaglandin E2 (PGE2)–degrading enzyme, as a hallmark of aged tissues, including skeletal muscle. The resulting reduction in PGE2 signaling is a major contributor to muscle atrophy in aged mice and results from 15-PGDH-expressing myofibers and interstitial cells within muscle. Inhibition of 15-PGDH, by targeted genetic knockdown or a small molecule inhibitor, increases aged muscle mass, strength, and exercise performance. These physiological benefits arise from rejuvenated PGE2 levels which augment mitochondrial function and autophagy and decrease TGF-beta and ubiquitin-proteasome pathways. Our studies demonstrate a previously unrecognized role for PGE2 signaling in countering muscle atrophy and identify 15-PGDH as a promising therapeutic target to counter sarcopenia.