In:
Science, American Association for the Advancement of Science (AAAS), Vol. 371, No. 6528 ( 2021-01-29)
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 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.
Type of Medium:
Online Resource
ISSN:
0036-8075
,
1095-9203
DOI:
10.1126/science.abc8059
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2021
detail.hit.zdb_id:
128410-1
detail.hit.zdb_id:
2066996-3
detail.hit.zdb_id:
2060783-0
SSG:
11
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