Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise.
Muscle-Specific Cellular and Molecular Adaptations to Late-Life Voluntary Concurrent Exercise.
复制标题
DOI：
10.1093/function/zqac027
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
小鼠运动模型可以提供信息的因素，影响肌肉的适应性与老化，但很少有可翻译的解决方案存在。渐进式负重轮跑（PoWeR）是一种简单、自愿、低成本、高容量的耐力/阻力运动方法，用于训练幼鼠。在本研究中，老年小鼠（22月龄）进行了8周的修改版本的PoWeR。肌肉功能、细胞、生物化学、转录和肌核DNA甲基化分析提供了老年小鼠肌肉如何对大容量综合训练做出反应的全面图片。小鼠每天跑6-8 km，相对于久坐的小鼠，PoWeR增加了跖屈肌的肌肉力量。老年小鼠的氧化比目鱼肌对PoWeR的反应与以前工作中测量的每个参数中的年轻小鼠相似;这包括肌肉质量、糖酵解到氧化纤维类型转换、纤维大小、卫星细胞频率和肌纤维数量。氧化/糖酵解足底肌根据纤维类型进行适应，但肌肉质量总体变化不大。毛细作用随着两种肌肉中的PoWeR而显著增加，这可能是老年适应性的许可。与已发表的年轻小鼠PoWeR RNA测序数据进行比较，确定了年龄和肌肉适应性的保守调节因子;这包括与肌肉血管系统相关的Aldh 1 l1。Agrn和Samd 1基因表达上调后PoWeR同时与低甲基化的启动子CpG myocardial DNA，这可能有影响神经支配和毛细血管化。Rbm 10中的启动子CpG通过晚年运动在肌核中低甲基化，与肌肉组织中的发现一致。PoWeR和本文的数据是揭示肌肉适应衰老的细胞和分子调节因子的资源。并行PoWeR训练可以作为一个简单有效的临床前平台，用于发现肌肉适应衰老的细胞和分子调节因子，从而推动发现衰老相关肌肉病理学的新疗法。
Murine exercise models can provide information on factors that influence muscle adaptability with aging, but few translatable solutions exist. Progressive weighted wheel running (PoWeR) is a simple, voluntary, low-cost, high-volume endurance/resistance exercise approach for training young mice. In the current investigation, aged mice (22-mo-old) underwent a modified version of PoWeR for 8 wk. Muscle functional, cellular, biochemical, transcriptional, and myonuclear DNA methylation analyses provide an encompassing picture of how muscle from aged mice responds to high-volume combined training. Mice run 6–8 km/d, and relative to sedentary mice, PoWeR increases plantarflexor muscle strength. The oxidative soleus of aged mice responds to PoWeR similarly to young mice in every parameter measured in previous work; this includes muscle mass, glycolytic-to-oxidative fiber type transitioning, fiber size, satellite cell frequency, and myonuclear number. The oxidative/glycolytic plantaris adapts according to fiber type, but with modest overall changes in muscle mass. Capillarity increases markedly with PoWeR in both muscles, which may be permissive for adaptability in advanced age. Comparison to published PoWeR RNA-sequencing data in young mice identified conserved regulators of adaptability across age and muscles; this includes Aldh1l1 which associates with muscle vasculature. Agrn and Samd1 gene expression is upregulated after PoWeR simultaneous with a hypomethylated promoter CpG in myonuclear DNA, which could have implications for innervation and capillarization. A promoter CpG in Rbm10 is hypomethylated by late-life exercise in myonuclei, consistent with findings in muscle tissue. PoWeR and the data herein are a resource for uncovering cellular and molecular regulators of muscle adaptation with aging. Concurrent PoWeR training can be leveraged as a simple and effective pre-clinical platform for discovering cellular and molecular regulators of muscle adaptation with aging, thereby driving the discovery of new therapeutics for aging-related muscle pathology
影响因子：
1.5
作者：
Layne AS;Krehbiel LM;Mankowski RT;Anton SD;Leeuwenburgh C;Pahor M;Sandesara B;Wu SS;Buford TW
通讯作者：
Buford TW