Department of Biology, University of Alabama at Birmingham Birmingham, AL, USA.
Front Genet. 2013 Aug 14;4:159. doi: 10.3389/fgene.2013.00159. eCollection 2013.
Sarcopenia and dynapenia pose significant problems for the aged, especially as life expectancy rises in developed countries. Current therapies are marginally efficacious at best, and barriers to breakthroughs in treatment may result from currently employed model organisms. Here, we argue that the use of indeterminate-growing teleost fish in skeletal muscle aging research may lead to therapeutic advancements not possible with current mammalian models. Evidence from a comparative approach utilizing the subfamily Danioninae suggests that the indeterminate growth paradigm of many teleosts arises from adult muscle stem cells with greater proliferative capacity, even in spite of smaller progenitor populations. We hypothesize that paired-box transcription factors, Pax3/7, are involved with this enhanced self-renewal and that prolonged expression of these factors may allow some fish species to escape, or at least forestall, sarcopenia/dynapenia. Future research efforts should focus on the experimental validation of these genes as key factors in indeterminate growth, both in the context of muscle stem cell proliferation and in prevention of skeletal muscle senescence.
肌肉减少症和动力不足症给老年人带来了重大问题，尤其是在发达国家预期寿命延长的情况下。目前的治疗方法最多只能起到轻微的效果，治疗突破的障碍可能源于目前使用的模式生物。在这里，我们认为在骨骼肌肉衰老研究中使用不定生长的硬骨鱼可能会带来目前哺乳动物模型不可能实现的治疗进展。利用 Danioninae 亚科进行比较研究的证据表明，许多硬骨鱼的不定生长模式源于具有更高增殖能力的成年肌肉干细胞，即使祖细胞群体较小也是如此。我们假设配对盒转录因子 Pax3/7 参与了这种增强的自我更新，并且这些因子的延长表达可能使一些鱼类物种能够逃避或至少延缓肌肉减少症/动力不足症的发生。未来的研究工作应集中在这些基因作为不定生长的关键因素的实验验证上，既要验证其在肌肉干细胞增殖方面的作用，也要验证其在预防骨骼肌肉衰老方面的作用。
