Abstract
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 2 = 0.297, P < 0.001, n = 57), and VO 2peak 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.
Highlights
In humans, aging impairs multiple biological processes from a molecular to organismal level, and affects mental and cardio-respiratory health (North and Sinclair 2012), body composition (Bischof and Park 2015), and muscle function (Curtis et al 2015)
Skeletal muscle nicotinamide phosphoribosyltransferase (NAMPT) abundance correlates with distinct physiological parameters Correlation analyses were used to determine whether baseline skeletal muscle NAMPT protein levels correlated with age and other parameters measured in the study
Aerobic and resistance exercise training increase human skeletal muscle NAMPT protein To determine if aerobic or resistance exercise training affected the abundance of the NAD+ salvage pathway enzymes, Western blot analyses for NAMPT, nicotinamide riboside kinase 2 (NRK2), NMNAT1, and NMNAT3 were performed in human vastus lateralis muscle biopsies before and after exercise training in both young (≤35 years old) and older (≥55 years old) participants
Summary
In humans, aging impairs multiple biological processes from a molecular to organismal level, and affects mental and cardio-respiratory health (North and Sinclair 2012), body composition (Bischof and Park 2015), and muscle function (Curtis et al 2015). Muscle morphology, fiber size, and functional properties including strength, are preserved by lifelong physical activity (Zampieri et al 2015) Both aerobic and resistance exercise training exert multiple beneficial effects on the aging body (Vopat et al 2014; Borde et al 2015; Milanovic et al 2015; Mancini et al 2017). Evidence is lacking regarding the potency of distinct modes of exercise training to increase NAD+ salvage enzyme levels in skeletal muscle and adipose tissue of young and older humans. To this end, we assessed the age-dependent effect of 12 weeks of either aerobic or resistance exercise training on skeletal muscle abundance of NAD+ salvage enzymes (i.e., NAMPT, NRK, and NMNATs). Our findings underscore the importance of regular physical activity to restore skeletal muscle NAD+ salvage capacity with age and have general implications for treatment of metabolic disease
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