Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.
Department of Biology, University of Padova, 35131 Padova, Italy.
Int J Mol Sci. 2021 Oct 30;22(21):11789. doi: 10.3390/ijms222111789.
Curcumin administration attenuates muscle disuse atrophy, but its effectiveness against aging-induced, selective loss of mass or force (presarcopenia or asthenia/dynopenia), or combined loss (sarcopenia), remains controversial. A new systemic curcumin treatment was developed and tested in 18-month-old C57BL6J and C57BL10ScSn male mice. The effects on survival, liver toxicity, loss of muscle mass and force, and satellite cell responsivity and commitment were evaluated after 6-month treatment. Although only 24-month-old C57BL10ScSn mice displayed age-related muscle impairment, curcumin significantly increased survival of both strains (+20-35%), without signs of liver toxicity. Treatment prevented sarcopenia in soleus and presarcopenia in EDL of C57BL10ScSn mice, whereas it did not affect healthy-aged muscles of C57BL6J. Curcumin-treated old C57BL10ScSn soleus preserved type-1 myofiber size and increased type-2A one, whereas EDL maintained adult values of total myofiber number and fiber-type composition. Mechanistically, curcumin only partially prevented the age-related changes in protein level and subcellular distribution of major costamere components and regulators. Conversely, it affected satellite cells, by maintaining adult levels of myofiber maturation in old regenerating soleus and increasing percentage of isolated, MyoD-positive satellite cells from old hindlimb muscles. Therefore, curcumin treatment successfully prevents presarcopenia and sarcopenia development by improving satellite cell commitment and recruitment.
姜黄素的应用可减轻肌肉失用性萎缩,但它对衰老引起的、选择性的质量或力量损失(前肌少症或乏力/动力不足),或联合损失(肌少症)的有效性仍存在争议。一种新的系统性姜黄素治疗方法已被开发并在 18 个月大的 C57BL6J 和 C57BL10ScSn 雄性小鼠中进行了测试。在 6 个月的治疗后,评估了对生存、肝毒性、肌肉质量和力量损失以及卫星细胞反应性和定向性的影响。尽管只有 24 个月大的 C57BL10ScSn 小鼠显示出与年龄相关的肌肉损伤,但姜黄素显著增加了两种品系的存活率(+20-35%),没有肝毒性的迹象。该治疗预防了 C57BL10ScSn 小鼠比目鱼肌的肌少症和 EDL 的前肌少症,但对 C57BL6J 的健康老年肌肉没有影响。姜黄素处理的老年 C57BL10ScSn 比目鱼肌保留了 1 型肌纤维的大小,并增加了 2A 型肌纤维的大小,而 EDL 保持了总肌纤维数量和纤维型组成的成人值。从机制上讲,姜黄素仅部分预防了主要成本体成分和调节剂的蛋白水平和亚细胞分布随年龄变化的情况。相反,它影响了卫星细胞,通过在老年再生比目鱼肌中维持肌纤维成熟的成人水平,并增加了来自老年后肢肌肉的分离、MyoD 阳性卫星细胞的百分比。因此,姜黄素治疗通过改善卫星细胞定向性和募集来成功预防前肌少症和肌少症的发展。