Healthy aging and muscle function are positively associated with NAD+ abundance in humans

Skeletal muscle is greatly affected by aging, resulting in a loss of metabolic and physical function. However, the underlying molecular processes and how (lack of) physical activity is involved in age-related metabolic decline in muscle function in humans is largely unknown. Here, we compared, in a cross-sectional study, the muscle metabolome from young to older adults, whereby the older adults were exercise trained, had normal physical activity levels or were physically impaired. Nicotinamide adenine dinucleotide (NAD(+)) was one of the most prominent metabolites that was lower in older adults, in line with preclinical models. This lower level was even more pronounced in impaired older individuals, and conversely, exercise-trained older individuals had NAD(+) levels that were more similar to those found in younger individuals. NAD(+) abundance positively correlated with average number of steps per day and mitochondrial and muscle functioning. Our work suggests that a clear association exists between NAD(+) and health status in human aging.

Automated summary

This study reveals the impact of aging on skeletal muscle function and metabolism, as well as the association between (lack of) physical activity and age-related decline in muscle function. The levels of nicotinamide adenine dinucleotide (NAD(+)) were found to be significantly lower in older adults, and this decrease was more pronounced in physically impaired individuals. However, exercise-trained older individuals had NAD(+) levels similar to those of younger individuals, indicating a positive effect of physical activity on NAD(+) abundance and muscle functioning.