Stewart C E H, Rittweger J
Institute for Biophysical and Clinical Research into Human Movement, Department of Exercise and Sport Science, MMU Cheshire, England, UK.
J Musculoskelet Neuronal Interact. 2006 Jan-Mar;6(1):73-86.
Skeletal muscle is a highly adaptable tissue. It responds to environmental and physiological challenges by changes in size, fibre type and metabolism. All of these responses are underpinned by our genes and it is therefore generally assumed that genetic variation between individuals may account for the differences in musculature and athletic capabilities between people. Research into the genetic influences of our muscle is at an embryonic stage, but some early insight into potential regulators has recently emerged, which is reflected in this review. Broad heritability, which appears to affect muscle size and strength more than metabolism has been assessed in twin and sibling studies. It appears to account for more inter-individual variation in the young as opposed to older people. However, the studies reported to date do demonstrate a large degree of diversity, which is probably predominantly due to different methodological approaches being adopted as well as distinct populations being studied. At a molecular level, there has been enormous progress in identifying regulators of atrophy and hypertrophy though the study of knock-out and transgenic animals and also through the utilisation of cell culture models. Among others, the insulin-like growth factors, calcineurin, desmin, myf5, mrf4, MyoD and myogenin have been identified as positive regulators of muscle size, while TNF-alpha, myostatin and components of the ubiquitin pathway have been recognized as regulators of muscle wasting. However, given the ethical and mechanistic constraints of performing similar studies in humans, difficulties have arisen when attempting to translate the animal and cell culture findings to humans. However, the current search for target "exercise genes" in humans has yielded the first successful results. Variations in the genes encoding for: the angiotensin converting enzyme, alpha-actinin 3, bradykinin, ciliary neurotrophic factor, interleukin-15, insulin-like growth factor II, myostatin and the vitamin D-receptor have all been found to account for some of the inter-subject variability in muscle strength or size. However, the influences of these genetic variations are somewhat weak, and not always reproducible and furthermore they are predominantly based in young healthy people. Hence, a key topic, namely the molecular mechanisms of muscle frailty in the elderly still remains to be elucidated.
骨骼肌是一种高度适应性的组织。它通过大小、纤维类型和代谢的变化来应对环境和生理挑战。所有这些反应都由我们的基因支撑，因此人们普遍认为个体之间的基因差异可能解释了人与人之间肌肉组织和运动能力的差异。对我们肌肉的遗传影响的研究尚处于起步阶段，但最近已出现了一些对潜在调节因子的初步见解，本综述对此有所体现。在双胞胎和兄弟姐妹研究中评估了广义遗传率，它似乎对肌肉大小和力量的影响比对代谢的影响更大。与老年人相比，它似乎在年轻人中解释了更多的个体间差异。然而，迄今为止报道的研究确实显示出很大程度的多样性，这可能主要是由于采用了不同的方法以及研究的人群不同。在分子水平上，通过对基因敲除和转基因动物的研究以及利用细胞培养模型，在识别萎缩和肥大的调节因子方面取得了巨大进展。其中，胰岛素样生长因子、钙调神经磷酸酶、结蛋白、肌原性决定因子5、肌肉调节因子4、肌源性分化抗原和肌细胞生成素已被确定为肌肉大小的正向调节因子，而肿瘤坏死因子-α、肌肉生长抑制素和泛素途径的成分已被认为是肌肉萎缩的调节因子。然而，鉴于在人类中进行类似研究存在伦理和机制上的限制，在试图将动物和细胞培养的研究结果转化到人类时出现了困难。然而，目前在人类中寻找目标“运动基因”已取得了首个成功结果。已发现编码血管紧张素转换酶、α-辅肌动蛋白3、缓激肽、睫状神经营养因子、白细胞介素-15、胰岛素样生长因子II、肌肉生长抑制素和维生素D受体的基因变异都在一定程度上解释了个体间肌肉力量或大小的差异。然而，这些基因变异的影响有些微弱，且并非总是可重复的，此外它们主要基于年轻健康人群。因此，一个关键主题，即老年人肌肉衰弱的分子机制仍有待阐明。
