Zhou Yu, Sharma Neel, Dukes David, Myzithras Maria B, Gupta Priyanka, Khalil Ashraf, Kahn Julius, Ahlberg Jennifer S, Hayes David B, Franti Michael, Criswell Tracy
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, 27157, USA.
Boehringer-Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA.
AAPS J. 2017 Mar;19(2):431-437. doi: 10.1208/s12248-016-0024-x. Epub 2016 Dec 6.
Loss of skeletal muscle mass and function results in loss of mobility for elderly patients. Novel therapies that can protect and/or restore muscle function during aging would have profound effects on the quality of life for this population. Growth differentiation factor 11 (GDF11) has been proposed as a "youthful" circulating factor that can restore cardiac, neural, and skeletal muscle functions in aging animals. However, conflicting data has been recently published that casts doubt on these assertions. We used a complex rat model of skeletal muscle injury that physiologically mimics injuries seen in patients; to investigate the ability of GDF11 and to enhance skeletal muscle regeneration after injury in older rats. Our data showed that GDF11 treatment resulted in a significant increase in tissue fibrosis, accompanied by attenuated functional recovery, as compared to animals treated with vehicle alone. GDF11 impaired the recovery of skeletal muscle function in older rats after injury.
骨骼肌质量和功能的丧失会导致老年患者行动能力下降。能够在衰老过程中保护和/或恢复肌肉功能的新型疗法将对这一人群的生活质量产生深远影响。生长分化因子11(GDF11)被认为是一种“年轻的”循环因子,可恢复衰老动物的心脏、神经和骨骼肌功能。然而,最近发表的相互矛盾的数据对这些说法提出了质疑。我们使用了一种复杂的大鼠骨骼肌损伤模型,该模型在生理上模拟了患者所见的损伤;以研究GDF11促进老年大鼠损伤后骨骼肌再生的能力。我们的数据表明,与仅用赋形剂处理的动物相比,GDF11处理导致组织纤维化显著增加,同时功能恢复减弱。GDF11损害了老年大鼠损伤后骨骼肌功能的恢复。