Goldspink Geoffrey
Molecular Tissue Repair Unit, Department of Surgery, Royal Free and University College Medical School, University of London, London, UK.
Rejuvenation Res. 2007 Sep;10(3):397-405. doi: 10.1089/rej.2007.0597.
Age-related muscle wasting and increased frailty is a major socioeconomic as well as a major medical problem. In our quest to extend the quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and prevent them falling and breaking bones that are brittle because of osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues and a vicious cycle is established when the muscles start to produce less force resulting in more bone loss and weakening of tendons. Another aspect that is less well appreciated is that muscle acts as a dynamic, metabolic store. In a traumatic situation, muscle provides amino acids to aid tissue repair processes and maintaining acid-base balance. At the present time there are strategies in addition to exercise for preventing age-related muscle wasting and these are briefly reviewed. Here, more attention is paid to the role of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and the discovery of mechano-growth factor (MGF). This is derived from the IGF-1 gene by alternative splicing and in the young is responsible for increasing contractile strength in response to exercise by activating the muscle satellite (stem) cells that kick-start local muscle repair and induce hypertrophy. Recent studies including gene transfer of this part of the IGF-1 gene and unique MGF peptides offer the prospect of treating muscle wasting during the aging process as well as muscle cachexia associated with many diseases.
与年龄相关的肌肉萎缩和身体虚弱加剧是一个重大的社会经济问题,也是一个重大的医学问题。在我们追求延长生活质量的过程中,充分增强老年人的力量非常重要,这样他们才能完成日常任务,并防止因骨质疏松而导致骨骼脆弱易骨折。肌肉产生的机械应变有助于维持其他肌肉骨骼组织,当肌肉开始产生较少力量,导致更多骨质流失和肌腱变弱时,就会形成恶性循环。另一个不太为人所知的方面是,肌肉充当动态的代谢储备库。在创伤情况下,肌肉提供氨基酸以帮助组织修复过程并维持酸碱平衡。目前,除了运动之外,还有一些预防与年龄相关的肌肉萎缩的策略,在此将对这些策略进行简要综述。这里将更多地关注生长激素/胰岛素样生长因子-1(GH/IGF-1)轴的作用以及机械生长因子(MGF)的发现。MGF是通过选择性剪接从IGF-1基因衍生而来,在年轻人中,它通过激活肌肉卫星(干)细胞来增加收缩强度,以响应运动,这些卫星细胞启动局部肌肉修复并诱导肥大。包括对IGF-1基因这一部分进行基因转移以及独特的MGF肽在内的最新研究,为治疗衰老过程中的肌肉萎缩以及与多种疾病相关的肌肉恶病质提供了前景。