Preserved capacity for satellite cell proliferation, regeneration, and hypertrophy in the skeletal muscle of healthy elderly men

Preserved capacity for satellite cell proliferation, regeneration, and hypertrophy in the skeletal muscle of healthy elderly men
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DOI:
10.1096/fj.202000196r
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发表时间:
2020-03-13
期刊:
影响因子:
4.8
通讯作者:
Mackey, Abigail L.
Mackey, Abigail L.
中科院分区:
生物学2区
文献类型:
--
作者:
Karlsen, Anders;Soendenbroe, Casper;Mackey, Abigail L.

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随着年龄的增长,迟钝的肌肉肥大和受损的再生能力被部分归因于卫星细胞(SC)功能障碍。然而,真正的肌肉再生在老年人身上还没有被研究过。对7名青年(20-31岁)和19名老年(60-73岁)男性一侧小腿股外侧肌(VL)进行200次电刺激偏心收缩,造成肌肉损伤。随后,对双腿进行了13周的阻力训练(RT),以了解其肥大能力。分别于放疗前、放疗后、术后第9天采集肌肉活检标本,进行免疫组织化学和RT-PCR检测。用MRI、DEXA和免疫组织化学方法评价心肌肥厚程度。总体而言,年轻人和老年人之间的反应令人惊讶地相似。ES后第9天,Pax7+SC数量增加一倍(P&lt;0.05),并伴有与基质、肌肉发生和神经支配相关的基因表达的实质性变化(P&lt;0.05)。放疗后,ES+RT组双腿VL横截面积增加15%(P<0.05),SCs/II型纤维增加2~4倍(P&lt;.001)。这些新发现共同展示了人类老年肌肉的“年轻”再生和肥大反应。此外,提高健康老年男性的SC利用率并不会增强随后的肌肉肥大反应。
Blunted muscle hypertrophy and impaired regeneration with aging have been partly attributed to satellite cell (SC) dysfunction. However, true muscle regeneration has not yet been studied in elderly individuals. To investigate this, muscle injury was induced by 200 electrically stimulated (ES) eccentric contractions of the vastus lateralis (VL) of one leg in seven young (20-31 years) and 19 elderly men (60-73 years). This was followed by 13 weeks of resistance training (RT) for both legs to investigate the capacity for hypertrophy. Muscle biopsies were collected Pre- and Post-RT, and 9 days after ES, for immunohistochemistry and RT-PCR. Hypertrophy was assessed by MRI, DEXA, and immunohistochemistry. Overall, surprisingly comparable responses were observed between the young and elderly. Nine days after ES, Pax7+ SC number had doubled (P < .05), alongside necrosis and substantial changes in expression of genes related to matrix, myogenesis, and innervation (P < .05). Post-RT, VL cross-sectional area had increased in both legs (15%, P < .05) and SCs/type II fiber had increased 2-4 times more with ES+RT vs RT alone (P < .001). Together these novel findings demonstrate "youthful" regeneration and hypertrophy responses in human elderly muscle. Furthermore, boosting SC availability in healthy elderly men does not enhance the subsequent muscle hypertrophy response to RT.