背景在衰老期间,肌肉干细胞(MuSCs)的功能下降,影响骨骼肌的功能和再生能力。临床前证据表明,烟酰胺核苷(NR)和蝶芪(PT)可以改善肌肉再生,例如,通过增加MuSC功能。这项研究的目的是研究补充NR和PT(NRPT)是否通过改善MuSC的募集来促进老年个体肌肉损伤后的骨骼肌再生。方法将32名老年人(55-80岁)随机分为每日补充NRPT(1,000mgNR和200mgPT)或匹配的安慰剂。开始补充后两周,骨骼肌损伤是由电诱导的偏心肌肉工作引起的。之前获得了骨骼肌活检,2小时后,受伤后2、8和30天。结果该方案诱导了大量骨骼肌损伤,并与肌红蛋白和肌酸激酶的释放有关,肌肉酸痛,组织水肿,肌肉力量下降。MuSC内容,扩散,细胞大小显示了受伤后对招募的大量需求,但不受NRPT的影响。此外,肌纤维面积的组织学分析,中央核,胚胎肌球蛋白重链没有NRPT补充作用。结论:每日补充1,000mgNR和200mgPT是安全的,但不能改善老年人对损伤或随后再生的肌肉恢复的补充或其他措施。试验注册临床试验.govNCT03754842。诺和诺德基金会(NNF17OC0027242)和诺和诺德基金会CBMR。
BACKGROUNDDuring aging, there is a functional decline in the pool of muscle stem cells (MuSCs) that influences the functional and regenerative capacity of skeletal muscle. Preclinical evidence has suggested that nicotinamide riboside (NR) and pterostilbene (PT) can improve muscle regeneration, e.g., by increasing MuSC function. The objective of this
study was to investigate if supplementation with NR and PT (NRPT) promotes skeletal muscle regeneration after muscle injury in elderly individuals by improved recruitment of MuSCs.METHODSThirty-two elderly individuals (55-80 years of age) were randomized to daily supplementation with either NRPT (1,000 mg NR and 200 mg PT) or matched placebo. Two weeks after initiation of supplementation, skeletal muscle injury was induced by electrically induced eccentric muscle work. Skeletal muscle biopsies were obtained before, 2 hours after, and 2, 8, and 30 days after injury.RESULTSA substantial skeletal muscle injury was induced by the protocol and associated with release of myoglobin and creatine kinase, muscle soreness, tissue edema, and a decrease in muscle strength. MuSC content, proliferation, and cell size revealed a large demand for recruitment after injury, but this was not affected by NRPT. Furthermore, histological analyses of muscle fiber area, central nuclei, and embryonic myosin heavy chain showed no NRPT supplementation effect.CONCLUSIONDaily supplementation with 1,000 mg NR and 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly individuals.TRIAL REGISTRATIONClinicalTrials.gov NCT03754842.FUNDINGNovo Nordisk Foundation (NNF17OC0027242) and Novo Nordisk Foundation CBMR.