Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Ave, Guangzhou, 510515, People's Republic of China.
Department of Orthopaedics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Mol Med. 2024 Nov 30;30(1):238. doi: 10.1186/s10020-024-00998-2.
The fibrogenic conversion of satellite cells contributes to the atrophy and fibrosis of skeletal muscle, playing a significant role in the pathogenesis of age-related sarcopenia. Melatonin, a hormone secreted by the pineal gland, exhibits anti-aging and anti-fibrotic effects in various conditions. However, the effect of melatonin on satellite cell fate and age-related sarcopenia remains under-explored. Here, we report that melatonin treatment mitigated the loss of muscle mass and strength in aged mice, replenished the satellite cell pool and curtailed muscle fibrosis. When primary SCs were cultured in vitro and subjected to aging induction via D-galactose, they exhibited a diminished myogenic potential and a conversion from myogenic to fibrogenic lineage. Notably, melatonin treatment effectively restored the myogenic potential and inhibited this lineage conversion. Furthermore, melatonin attenuated the expression of the fibrogenic cytokine, transforming growth factor-β1, and reduced the phosphorylation of its downstream targets Smad2/3 both in vivo and in vitro. In summary, our findings show melatonin's capacity to counteract muscle decline and inhibit fibrogenic conversion in aging SCs and highlight its potential therapeutic value for age-related sarcopenia.
卫星细胞的纤维生成转化有助于骨骼肌的萎缩和纤维化，在与年龄相关的肌肉减少症的发病机制中起重要作用。褪黑素是松果腺分泌的一种激素，在各种情况下都具有抗衰老和抗纤维化作用。然而，褪黑素对卫星细胞命运和与年龄相关的肌肉减少症的影响仍未得到充分探索。在这里，我们报告褪黑素治疗减轻了老年小鼠的肌肉质量和力量损失，补充了卫星细胞池，并减少了肌肉纤维化。当原代 SC 在体外培养并通过 D-半乳糖诱导衰老时，它们的成肌潜能降低，并从成肌向纤维生成谱系转化。值得注意的是，褪黑素治疗可有效恢复成肌潜能并抑制这种谱系转化。此外，褪黑素在体内和体外均减弱了纤维生成细胞因子转化生长因子-β1 的表达，并降低了其下游靶标 Smad2/3 的磷酸化。总之，我们的研究结果表明褪黑素能够抵抗肌肉衰退并抑制衰老 SC 中的纤维生成转化，并突出了其治疗与年龄相关的肌肉减少症的潜在价值。
