Mitochondria provide chemical energy stores to power cellular operations, particularly vital in energy-hungry tissues such as brain and muscles. One portion of the decline in mitochondrial function in old age is characterized by loss of NAMPT and NAD+, though how exactly underlying damage that causes aging leads to this decline is unclear. It is known that a sizable fraction of the observed loss of muscle mass and strength with aging is avoidable, in the sense that it is possible to maintain strength and fitness until quite late in life, but most people choose not to put in the required effort. Losses can even be reversed when sedentary people take up exercise. Given this, it may not be surprising to find that exercise can restore NAMPT and NAD+ in older adults, which is something to bear in mind when considering the many groups selling supplements to enhance NAD+ levels.
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, and VO2peak 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.
Here we provide evidence that various exercise training modalities completely correct the age-dependent decline in skeletal muscle NAMPT abundance. Conversely, neither age nor exercise training affect levels of adipose tissue NAD+ salvage enzymes. 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.