Soendenbroe Casper, Schjerling Peter, Bechshøft Cecilie J L, Svensson Rene B, Schaeffer Laurent, Kjaer Michael, Chazaud Bénédicte, Jacquier Arnaud, Mackey Abigail L
Department of Orthopedic Surgery, Institute of Sports Medicine Copenhagen, Copenhagen University Hospital-Bispebjerg and Frederiksberg, Copenhagen, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Aging Cell. 2025 Mar;24(3):e14413. doi: 10.1111/acel.14413. Epub 2024 Nov 18.
Exercise preserves neuromuscular function in aging through unknown mechanisms. Skeletal muscle fibroblasts (FIB) and stem cells (MuSC) are abundant in skeletal muscle and reside close to neuromuscular junctions, but their relative roles in motor neuron maintenance remain undescribed. Using direct cocultures of embryonic rat motor neurons with either human MuSC or FIB, RNA sequencing revealed profound differential regulation of the motor neuron transcriptome, with FIB generally favoring neuron growth and cell migration and MuSC favoring production of ribosomes and translational machinery. Conditioned medium from FIB was superior to MuSC in preserving motor neurons and increasing their maturity. Lastly, we established the importance of donor age and exercise status and found an age-related distortion of motor neuron and muscle cell interaction that was fully mitigated by lifelong physical activity. In conclusion, we show that human muscle FIB and MuSC synergistically stimulate the growth and viability of motor neurons, which is further amplified by regular exercise.
运动通过未知机制维持衰老过程中的神经肌肉功能。骨骼肌成纤维细胞（FIB）和干细胞（MuSC）在骨骼肌中丰富存在且位于神经肌肉接头附近，但其在运动神经元维持中的相对作用仍未得到描述。通过将胚胎大鼠运动神经元与人类MuSC或FIB进行直接共培养，RNA测序揭示了运动神经元转录组的深刻差异调节，FIB通常有利于神经元生长和细胞迁移，而MuSC有利于核糖体和翻译机制的产生。FIB的条件培养基在保护运动神经元和提高其成熟度方面优于MuSC。最后，我们确定了供体年龄和运动状态的重要性，并发现运动神经元与肌肉细胞相互作用存在与年龄相关的扭曲，而终身体育活动可完全缓解这种扭曲。总之，我们表明人类肌肉FIB和MuSC协同刺激运动神经元的生长和活力，而规律运动可进一步增强这种作用。
