PRE-OPERATIVE TREATMENT WITH ELECTRICAL STIMULATION ENHANCES AGED MUSCLE REGENERA

衰老的肌肉在损伤后表现出骨骼肌再生能力降低。进步者 随着年龄的增长，肌肉力量的下降会导致功能活动能力受损，而肌肉无力与摔倒的可能性增加有关。年龄增加通常会导致骨骼肌对损伤的整体再生减少[5-7]，这进一步导致肌肉质量减少和虚弱[5]，增加对复发性肌肉损伤的易感性[8；9]，并延长恢复时间[io；ii]。衰老的骨骼肌表现出从年轻人常见的功能性肌纤维修复向纤维化形成的“快速修复”默认的转变。损伤后纤维化的形成与 肌肉无力[12]和损伤复发增加[13]。 肌肉前体细胞(MPC)，这些细胞主要负责骨骼肌再生， 显示在老年肌肉中肌源性向纤维性转化增加[2]。此转换需要一个 驻留细胞恢复过期细胞的原始功能和结构的能力发生变化。跟随 损伤后，MPC似乎主要分化为纤维化前体细胞，即成纤维细胞。来自我们的最新发现 实验室已经证明，损伤后纤维化的形成与 骨骼肌血管[14]。此外，伴随着MPC数量的显著减少。 随着年龄的增长[15-17]，这种减少可能与衰老骨骼肌的血管供应减少有关。 人类骨骼肌中的MPC数量已被证明与血管数量呈线性相关，MPC 研究发现，壁龛与血管相邻，且与毛细血管定位非随机相关[18]。 因此，导致血管减少的肌病被证明与成比例的 MPC的减少[18]。肌源性向纤维性转化似乎也与肌肉血管有关。 供应和体外异时研究，在这些研究中，从老年动物中分离出的MPC暴露于“幼年” 血清表现出显著增加的肌原性和降低的纤维化转化率[3：19]。这些 研究结果表明，与年龄相关的MPC肌原性下降是可逆的，内在因素控制着 MPC的命运对外界刺激有反应[3]。

Aged muscle displays decreased skeletal muscle regenerative capacity after injury. A progressive decline in muscle strength with age contributes to impaired ftmctional mobility, and muscle weakness has been associated with increased likelihood for falls [4]). Increasing age typically results in a decreased overall skeletal muscle regeneration in response to injury [5-7], which further contributes to the decreased muscle mass and weakness [5], increased susceptibility to recurrent muscle injury [8;9], and prolonged recovery [io;ii]. Aging skeletal muscle demonstrates a shift from functional myofiber repair, as is typically seen in young individuals, to a "quick-fix" default towards fibrosis formation. Fibrosis formation after injury has been associated with muscle weakness [12] and an increased injury recurrence [13]. Muscle precursor cells (MPCs), those cells predominantly responsible for skeletal muscle regeneration, demonstrate an increased myogenic-to-fibrogenic conversion in aged muscle [2]. This conversion entails a shift in the resident cell's ability to restore the original function and structure of expired cells. Following injury, MPCs appear to largely differentiate into fibrosis precursor cells, fibroblasts. Recent findings from our laboratory have demonstrated that fibrosis formation after injury is significantly and inversely correlated with skeletal muscle vascularity [14]. Moreover, a significant decrease in the number of MPCs is concomitant with. increasing age [15-17], a decrease that may be related to a reduced vascular supply of aged skeletal muscle. MPC numbers in human skeletal muscle have been shown to correlate linearly with vascularity, and MPC niches were found to be juxtavascular and non-randomly associated with capillary localization [18]. Accordingly, myopathies resulting in decreased vascularity were shown to be associated with a proportionate decrease in MPCs [18]. Myogenic-to-fibrogenic conversion also appears to be related to the muscle vascular supply, and in vitro heterochronic studies, in which MPCs isolated from aged animals are exposed to "young" serum demonstrate significantly increased myogenicity and a decreased fibrotic conversion [3:19]. These findings suggest that the age-related decline in MPC myogenicity is reversible, and intrinsic factors controlling MPC fate are responsive to extrinsic stimuli [3].