de Guia Roldan M, Agerholm Marianne, Nielsen Thomas S, Consitt Leslie A, Søgaard Ditte, Helge Jørn W, Larsen Steen, Brandauer Josef, Houmard Joseph A, Treebak Jonas T
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Biomedical Sciences, Ohio Musculoskeletal and Neurological Institute, Diabetes Institute, Ohio University, Athens, Ohio.
Physiol Rep. 2019 Jul;7(12):e14139. doi: 10.14814/phy2.14139.
Aging decreases skeletal muscle mass and strength, but aerobic and resistance exercise training maintains skeletal muscle function. NAD is a coenzyme for ATP production and a required substrate for enzymes regulating cellular homeostasis. In skeletal muscle, NAD is mainly generated by the NAD salvage pathway in which nicotinamide phosphoribosyltransferase (NAMPT) is rate-limiting. NAMPT decreases with age in human skeletal muscle, and aerobic exercise training increases NAMPT levels in young men. However, whether distinct modes of exercise training increase NAMPT levels in both young and old people is unknown. We assessed the effects of 12 weeks of aerobic and resistance exercise training on skeletal muscle abundance of NAMPT, nicotinamide riboside kinase 2 (NRK2), and nicotinamide mononucleotide adenylyltransferase (NMNAT) 1 and 3 in young (≤35 years) and older (≥55 years) individuals. NAMPT in skeletal muscle correlated negatively with age (r = 0.297, P < 0.001, n = 57), and VO peak was the best predictor of NAMPT levels. Moreover, aerobic exercise training increased NAMPT abundance 12% and 28% in young and older individuals, respectively, whereas resistance exercise training increased NAMPT abundance 25% and 30% in young and in older individuals, respectively. None of the other proteins changed with exercise training. In a separate cohort of young and old people, levels of NAMPT, NRK1, and NMNAT1/2 in abdominal subcutaneous adipose tissue were not affected by either age or 6 weeks of high-intensity interval training. Collectively, exercise training reverses the age-dependent decline in skeletal muscle NAMPT abundance, and our findings highlight the value of exercise training in ameliorating age-associated deterioration of skeletal muscle function.
衰老会降低骨骼肌质量和力量，但有氧运动和抗阻运动训练可维持骨骼肌功能。NAD是ATP生成的辅酶，也是调节细胞内稳态的酶所需的底物。在骨骼肌中，NAD主要由NAD补救途径生成，其中烟酰胺磷酸核糖基转移酶（NAMPT）是限速酶。在人类骨骼肌中，NAMPT水平会随年龄增长而降低，有氧运动训练可提高年轻男性的NAMPT水平。然而，不同的运动训练方式是否能提高年轻人和老年人的NAMPT水平尚不清楚。我们评估了12周的有氧运动和抗阻运动训练对年轻（≤35岁）和老年（≥55岁）个体骨骼肌中NAMPT、烟酰胺核糖激酶2（NRK2）以及烟酰胺单核苷酸腺苷酸转移酶（NMNAT）1和3含量的影响。骨骼肌中的NAMPT与年龄呈负相关（r = 0.297，P < 0.001，n = 57），VO峰值是NAMPT水平的最佳预测指标。此外，有氧运动训练分别使年轻和老年个体的NAMPT含量提高了12%和28%，而抗阻运动训练分别使年轻和老年个体的NAMPT含量提高了25%和30%。其他蛋白质的含量均未因运动训练而改变。在另一组年轻和老年人群中，腹部皮下脂肪组织中NAMPT、NRK1和NMNAT1/2的水平不受年龄或6周高强度间歇训练的影响。总体而言，运动训练可逆转骨骼肌中NAMPT含量随年龄增长而下降的趋势，我们的研究结果凸显了运动训练在改善与年龄相关的骨骼肌功能衰退方面的价值。
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