Chen Haiyun, Ren Biqi, Wang Jing, Liu Xingchen, Yi Xiangjiao, Goltzman David, Miao Dengshun
Department of Plastic Surgery, Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China.
Department of Topographic Anatomy, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang, People's Republic of China.
Aging (Albany NY). 2025 Mar 31;17(4):1026-1042. doi: 10.18632/aging.206232.
Sarcopenia, characterized by an age-related decline in skeletal muscle mass and function, is closely linked to vitamin D deficiency. This study examines the role of Sirtuin 1 (Sirt1) and its regulation by vitamin D in preventing sarcopenia. Utilizing wild-type, 1α-hydroxylase knockout (1α(OH)ase), and Sirt1 transgenic (Sirt1) 1α(OH)ase mice, we investigated muscle Sirt1 levels, muscle mass, fiber type, and senescence markers. Our results demonstrated that 1,25-Dihydroxyvitamin D (1,25(OH)2D3) upregulated Sirt1 and myogenic factor MyoD1 expression in C2C12 myoblasts via VDR-mediated transcription. Sirt1 overexpression in mesenchymal stem cells (MSCs) significantly mitigated muscle mass reduction, improved fiber cross-sectional area, and increased type II fiber numbers in 1α(OH)ase mice. Mechanistically, 1,25(OH)2D3 promoted muscle cell health by enhancing Sirt1 expression, which in turn reduced muscle cell senescence and the senescence-associated secretory phenotype (SASP) through decreased levels of acetylated nuclear p53 and p65, maintaining their cytoplasmic localization. Additionally, Sirt1 overexpression accelerated muscle regeneration post-injury by increasing embryonic myosin heavy chain expression and cell proliferation. These findings underscore the therapeutic potential of targeting vitamin D and Sirt1 pathways to prevent sarcopenia, suggesting that supplementation with active vitamin D and consequent Sirt1 activation could be effective strategies for managing age-related muscle wasting.
肌肉减少症的特征是骨骼肌质量和功能随年龄增长而下降，与维生素D缺乏密切相关。本研究探讨了沉默调节蛋白1（Sirt1）的作用及其受维生素D的调节在预防肌肉减少症中的作用。利用野生型、1α-羟化酶基因敲除（1α(OH)ase）和Sirt1转基因（Sirt1）1α(OH)ase小鼠，我们研究了肌肉Sirt1水平、肌肉质量、纤维类型和衰老标志物。我们的结果表明，1,25-二羟基维生素D（1,25(OH)2D3）通过维生素D受体（VDR）介导的转录上调C2C12成肌细胞中Sirt1和生肌因子MyoD1的表达。间充质干细胞（MSCs）中Sirt1的过表达显著减轻了1α(OH)ase小鼠的肌肉质量减少，改善了纤维横截面积，并增加了II型纤维数量。机制上，1,25(OH)2D3通过增强Sirt1表达促进肌肉细胞健康，进而通过降低乙酰化核p53和p65的水平减少肌肉细胞衰老和衰老相关分泌表型（SASP），使其维持在细胞质定位。此外，Sirt1过表达通过增加胚胎肌球蛋白重链表达和细胞增殖加速损伤后肌肉再生。这些发现强调了靶向维生素D和Sirt1通路预防肌肉减少症的治疗潜力，表明补充活性维生素D及随之激活Sirt1可能是管理与年龄相关的肌肉萎缩的有效策略。
