M309, School of Anatomy and Human Biology, The University of Western Australia, Perth, Western Australia.
Biogerontology. 2010 Jun;11(3):363-76. doi: 10.1007/s10522-009-9260-0. Epub 2009 Dec 24.
The ability of very old animals to make new muscle after injury remains controversial. This issue has major implications for the regenerative potential of damaged geriatric human muscle, to age-related loss of muscle mass (sarcopenia) and to the proposed need for muscle stem cell therapy for the aged. To further address issues of inherent myogenic capacity and the role of host systemic factors in new muscle formation, whole muscle grafts were transplanted between geriatric (aged 27-29 months) and young (3 months) C57Bl/6J mice and compared with autografts in geriatric and young mice. Grafts were sampled at 5 and 10 days for histological analysis. Inflammation and formation of new myotubes was strikingly impaired at 5 days in the geriatric muscle autografts. However, there was a strong inflammatory response by the geriatric hosts to young muscle grafts and geriatric muscles provoked an inflammatory response by young hosts at 5 days. At 10 days, extensive myotube formation in geriatric muscle autografts (equivalent to that seen in young autografts and both other groups) confirmed excellent intrinsic capacity of myogenic (stem) cells to proliferate and fuse. The key conclusion is that a weaker chemotactic stimulus by damaged geriatric muscle, combined with a reduced inflammatory response of old hosts, results in delayed inflammation in geriatric muscle autografts. This delay is transient. Once inflammation occurs, myogenesis can proceed. The presence of well developed myotubes in old muscle autografts at 10 days confirms a very good inherent myogenic response of geriatric skeletal muscle.
非常老的动物在受伤后产生新肌肉的能力仍然存在争议。这个问题对受损老年人类肌肉的再生潜力、与年龄相关的肌肉质量损失（肌肉减少症）以及为老年人群体提出的肌肉干细胞治疗的必要性都有重大影响。为了进一步解决固有成肌能力的问题以及宿主系统性因素在新肌肉形成中的作用，将整个肌肉移植物从老年（27-29 个月）和年轻（3 个月）C57Bl/6J 小鼠之间移植，并与老年和年轻小鼠的自体移植物进行比较。在第 5 天和第 10 天对移植物进行组织学分析。在第 5 天，老年肌肉自体移植物中的炎症和新肌管形成明显受损。然而，老年宿主对年轻肌肉移植物有强烈的炎症反应，老年宿主对年轻肌肉也有炎症反应。在第 10 天，老年肌肉自体移植物中广泛形成肌管（与年轻自体移植物和其他两组所见相同）证实了成肌（干）细胞增殖和融合的极好固有能力。关键结论是，受损老年肌肉的趋化刺激较弱，加上老年宿主的炎症反应降低，导致老年肌肉自体移植物中的炎症延迟。这种延迟是短暂的。一旦发生炎症，肌生成就可以进行。10 天时老年肌肉自体移植物中存在发育良好的肌管证实了老年骨骼肌具有非常好的固有成肌反应。
