Resistance training increases muscle NAD+ and NADH concentrations as well as NAMPT protein levels and global sirtuin activity in middle-aged, overweight, untrained individuals.

Donald A Lamb,Andrew D Fruge,Michael D Goodlett,Johnathon H Moore,Carlton D Fox,Tim N Ziegenfuss,Christopher G Vann,Michael D Roberts,Kaelin C Young,Paulo Henrique Caldeira Mesquita,Shelby C Osburn,Morgan A Smith,Kevin W Huggins,Andreas N Kavazis,Hector L Lopez

doi:10.18632/aging.103218

Donald A Lamb, Andrew D Fruge + Show 13 more

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https://doi.org/10.18632/aging.103218

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Journal: Aging	Publication Date: May 5, 2020
Citations: 39	License type: cc-by

Affiliation: Auburn University

Abstract

We examined if resistance training affected muscle NAD+ and NADH concentrations as well as nicotinamide phosphoribosyltransferase (NAMPT) protein levels and sirtuin (SIRT) activity markers in middle-aged, untrained (MA) individuals. MA participants (59±4 years old; n=16) completed 10 weeks of full-body resistance training (2 d/wk). Body composition, knee extensor strength, and vastus lateralis muscle biopsies were obtained prior to training (Pre) and 72 hours following the last training bout (Post). Data from trained college-aged men (22±3 years old, training age: 6±2 years old; n=15) were also obtained for comparative purposes. Muscle NAD+ (+127%, p<0.001), NADH (+99%, p=0.002), global SIRT activity (+13%, p=0.036), and NAMPT protein (+15%, p=0.014) increased from Pre to Post in MA participants. Additionally, Pre muscle NAD+ and NADH in MA participants were lower than college-aged participants (p<0.05), whereas Post values were similar between cohorts (p>0.10). Interestingly, muscle citrate synthase activity levels (i.e., mitochondrial density) increased in MA participants from Pre to Post (+183%, p<0.001), and this increase was significantly associated with increases in muscle NAD+ (r2=0.592, p=0.001). In summary, muscle NAD+, NADH, and global SIRT activity are positively affected by resistance training in middle-aged, untrained individuals. Whether these adaptations facilitated mitochondrial biogenesis remains to be determined.

Highlights

Nicotinamide adenine dinucleotide (NAD+) is a metabolite involved in numerous biochemical reactions
Middle-aged participants were 59±4 years of age, and possessed a body mass index (BMI) of 31.7±5.6 kg/m2, possessed a fat-free mass index (FFMi; dual x-ray absorptiometry (DXA) FFM in kg divided by height in m2) of 18.0±2.9 kg/m2, and possessed a body fat percentage of 39.3±6.3%
In MA participants, no significant gender×time interactions existed for Pre to Post changes in muscle NAD+ concentrations (p=0.099), Figure 1

Summary

Introduction

Nicotinamide adenine dinucleotide (NAD+) is a metabolite involved in numerous biochemical reactions. NAD+ concentrations play in the aging process (reviewed in [1,2,3]), and researchers have determined skeletal muscle NAD+ concentrations are lower in older rodents and humans [4,5,6] These findings have led some to suggest that the age-associated loss in skeletal muscle NAD+ levels contributes to mitochondrial dysfunction (reviewed in [7]). There is evidence to suggest skeletal muscle NAMPT protein levels are lower in older versus younger humans [11], and this finding re-iterates the notion that maintaining skeletal muscle NAD+ concentrations may be integral in maintaining metabolic homeostasis

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