Reduced expression of calcitonin receptor is closely associated with age-related loss of the muscle stem cell pool.
Reduced expression of calcitonin receptor is closely associated with age-related loss of the muscle stem cell pool.
复制标题
降钙素受体表达的减少与年龄相关的肌肉干细胞库的丧失密切相关。
DOI：
10.1002/j.2617-1619.2019.tb00012.x
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
So-ichiro Fukada
中科院分区：
文献类型：
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作者：
Madoka Ikemoto-Uezumi;Akiyoshi Uezumi;Lidan Zhang;Heying Zhou;Naohiro Hashimoto;Kikuo Okamura;Yasumoto Matsui;Koji Tsukazaki;Tohru Hosoyama;Masashi Nakatani;Mitsuhiro Morita;Harumoto Yamada;Kunihiro Tsuchida;So-ichiro Fukada
随着年龄的增长，肌肉的再生能力会下降。肌肉干细胞（MuSC）池的下降被认为是与年龄相关的肌肉再生不足的原因。然而，musc数量随年龄增长而减少的原因尚不清楚。我们之前发现降钙素受体（Calcr）由MuSC表达，并在维持MuSC库中起关键作用。在这项研究中，我们研究了Calcr是否与年龄相关的MuSC数量减少有关。方法和结果采用免疫荧光染色法测定出生后生长和衰老过程中肌组织中scalcr的表达。利用小鼠肌原系细胞条件删除Calcr，研究了Calcr在发育、出生后生长和成年期的作用。为了探讨Calcr信号在年龄相关的MuSC数量变化中的意义，我们检测了内源性Calcr配体的表达水平。免疫组织学检查显示，随着musc进入静止状态，Calcr表达增强。早期肌系细胞的条件Calcr缺失不影响MuSC池的初始容量，但会促进年龄依赖性MuSC损失。内源性Calcr配体的表达随年龄的增长保持不变。然而，与小鼠和人类的年轻肌肉相比，老年肌肉中Calcr的表达明显下降，并且这种下降伴随着musc的缺失。sour研究显示，随着年龄的增长，MuSC中钙含量显著降低，这可能导致MuSC池的年龄相关损失。因此，Calcr信号可能是预防衰老相关肌肉再生不足的一个有希望的靶点。
BackgroundMuscle regenerative capacity reduces during aging. Decline in the muscle stem cell (MuSC) pool is thought to be a cause of age‐related muscle regeneration insufficiency. However, why the number of MuSCs decreases with age remains unclear. We previously found that the calcitonin receptor (Calcr) is expressed by MuSCs and plays a pivotal role in maintaining the MuSC pool. In this study, we examined whether Calcr is involved in the age‐related decrease in MuSC number.Methods and resultsCalcr expression in MuSCs was assessed by immunofluorescence staining using muscle sections during postnatal growth and during aging. The role of Calcr during development, postnatal growth and adult stage was examined using mice conditionally deleted Calcr in myogenic lineage cells. To explore the significance of Calcr signaling on age‐related changes in MuSC number, expression levels of endogenous Calcr ligands were examined. Immunohistological examination revealed that Calcr expression grew stronger as MuSCs became quiescent. Conditional Calcr deletion in early myogenic lineage cells did not affect the initial capacity of the MuSC pool, but promoted age‐dependent MuSC loss. Expression of endogenous Calcr ligands remained unchanged with aging. Calcr expression in MuSCs, however, decreased significantly in aged muscle compared with young muscle in both mice and humans, and this reduction was accompanied by a loss of MuSCs.ConclusionsOur study revealed significant reduction of Calcr in MuSCs with age, possibly leading to age‐related loss of the MuSC pool. Thus, Calcr signaling could represent a promising target for preventing aging‐associated muscle regeneration insufficiency.