美国斯坦福医学院H. M. Blau团队取得最新进展。他们表明抑制前列腺素降解酶15-PGDH可使衰老的肌肉质量和力量恢复活力。相关论文于2020年12月10日发表在《科学》杂志上。

他们发现升高的15-PGDH（前列腺素E2（PGE2）降解酶）是包括骨骼肌在内的衰老组织的标志。PGE2信号转导的减少是衰老小鼠肌肉萎缩的主要原因，这是由表达15-PGDH的肌纤维和肌肉中的间质细胞引起的。通过靶向基因敲除或小分子抑制剂抑制15-PGDH可以增加衰老的肌肉质量、力量和运动表现。

这些生理益处来自恢复活力的PGE2水平，PGE2水平增强线粒体功能和自噬，并降低TGF-β和泛素-蛋白酶体途径。他们的研究证明了PGE2信号在对抗肌肉萎缩方面以前未被认识的作用，并确定15-PGDH是对抗肌肉减少症的潜在治疗靶标。

据介绍，肌肉减少症治疗方法较少，肌肉减少症是与衰老有关的骨骼肌消耗综合症。

附：英文原文

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

Author: A. R. Palla, M. Ravichandran, Y. X. Wang, L. Alexandrova, A. V. Yang, P. Kraft, C. A. Holbrook, C. M. Schürch, A. T. V. Ho, H. M. Blau

Issue&Volume: 2020/12/10

Abstract: 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.

DOI: 10.1126/science.abc8059

Source: https://science.sciencemag.org/content/early/2020/12/09/science.abc8059