Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength.
Science
; 371(6528)2021 01 29.
Article
en En
| MEDLINE
| ID: mdl-33303683
ABSTRACT
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-ß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rejuvenecimiento
/
Envejecimiento
/
Dinoprostona
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Hidroxiprostaglandina Deshidrogenasas
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Músculo Esquelético
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Sarcopenia
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos