Aerobic and resistance exercise training reverses age‐dependent decline in NAD⁺salvage capacity in human skeletal muscle

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 ( NRK 2), 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 2 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 , NRK 1, and NMNAT 1/2 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.

Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin‐resistant men

“…Moreover, , M‐value and lean body mass correlate positively with skeletal muscle NAMPT levels (de Guia et al . ). To determine if similar associations were present in the current study, we correlated all parameters measured in the participants before treatment with NAMPT abundance.…”

“…These observations are in line with previous results showing negative associations between NAMPT in skeletal muscle and age, BMI, fat body mass as well as with total cholesterol and LDL (de Guia et al . ). In contrast, , M‐value and lean body mass were found to correlate positively with NAMPT concentration in that study.…”

“…; de Guia et al . ) increase NAMPT levels in subcutaneous adipose tissue and skeletal muscle, respectively.…”

“…None of these correlations were significant (data not shown). We recently reported that NAMPT in human skeletal muscle correlates negatively with age, BMI, fat mass, and total cholesterol and low-density lipoprotein (LDL) (de Guia et al 2019). Moreover, V O 2 peak , M-value and lean body mass correlate positively with skeletal muscle NAMPT levels (de Guia et al 2019).…”

“…In humans, an age-associated decline of NAD + levels has been observed in liver (Zhou et al 2016), skin (Massudi et al 2012) and brain (Zhu et al 2015). Meanwhile, health-promoting lifestyle interventions such as a weight loss-promoting diet (Rappou et al 2016) and exercise (Costford et al 2010;Brandauer et al 2013;de Guia et al 2019) increase NAMPT levels in subcutaneous adipose tissue and skeletal muscle, respectively.…”