Fusion of dysfunction muscle stem cells with myofibers induces sarcopenia in mice.
Fusion of dysfunction muscle stem cells with myofibers induces sarcopenia in mice.
复制标题
功能障碍的肌肉干细胞与肌纤维的融合会诱发小鼠肌肉减少症。
DOI：
10.1101/2023.01.20.524967
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mishra,Prashant
中科院分区：
文献类型：
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作者：
Wang,Xun;Mishra,Prashant
肌肉减少症，或与年龄相关的肌肉萎缩，是一种进行性疾病，影响约10-30%的老年人口（1,2）。已经提出了许多导致肌肉减少症的因素，包括肌肉干细胞（musc）随着年龄的增长而逐渐丧失。然而，对小鼠的研究已经证明，MuSC消耗并不足以诱导肌肉减少症（3,4）。我们最近发现，在与年龄相关的线粒体损伤的反应中，MuSCs通过与邻近的肌纤维融合而自我移除，从而耗尽受损祖细胞的干细胞群(5)。在这里，我们发现musc -肌纤维融合足以引发小鼠肌纤维萎缩，从而限制了它们的运动功能和寿命。相反，抑制musc -肌纤维融合可阻止肌纤维随年龄增长而萎缩，从而增加动物的最大寿命。这些发现表明，受损的MuSC与成年肌纤维的积累融合是肌肉减少症的关键驱动特征，并解决了MuSC消耗本身不会引发肌纤维萎缩的发现。
Sarcopenia, or age-associated muscle atrophy, is a progressive condition which affects ~10–30% of the human geriatric population (1, 2). A number of contributors to sarcopenia have been proposed, including the progressive loss of muscle stem cells (MuSCs) with age. However, studies in mice have provided evidence that MuSC depletion is not sufficient to induce sarcopenia (3, 4). We recently showed that in response to age-associated mitochondrial damage, MuSCs self-remove by fusing with neighboring myofibers, which depletes the stem cell population of damaged progenitors (5). Here, we show that MuSC-myofiber fusion is sufficient to initiate myofiber atrophy in mice, which limits their motor function and lifespan. Conversely, inhibition of MuSC-myofiber fusion blocks myofiber atrophy with age, with a concomitant increase in the maximum lifespan of animals. These findings suggest a model where the accumulation fusion of damaged MuSCs with adult myofibers is a key driving feature of sarcopenia, and resolves the findings that MuSC depletion on its own does not initiate myofiber atrophy.