As people grow older skeletal muscle gradually becomes smaller and weaker, causing reduced mobility and quality of life. To understand and reverse this negative process investigators need to find new ways of improving the ability of muscle to perform physical activity. There is some evidence that supplements may improve how the mitochondria work, and investigators want to explore this idea in more detail, by measuring how the muscles work and respond to exercise before and after taking the supplement. This will give us the basic information investigators would need to see if this is a useful idea.

A defining feature of ageing is loss of muscle mass ('sarcopenia') and associated functional weakness ('dynapenia'). A common characteristic of dynapenia is lowered mitochondrial content and metabolic function, causing reduced aerobic capacity, increased sensations of effort and impaired lipid oxidation (with resultant glucose intolerance). Exercise training improves mitochondrial and muscle function in ageing populations, however such adaptations remain below that of young counterparts, suggesting alternative approaches are required. Pre-clinical studies show that dietary supplementation with precursors of nicotinamide adenine dinucleotide (NAD+) restore mitochondrial biogenesis and oxidative capacity in ageing rodents and diabetic humans. However, whether NAD+ precursors rejuvenate mitochondrial capacity and, ultimately, muscle function in older humans is unknown. This pilot project will therefore investigate the efficacy of NAD+ precursor supplementation for increasing muscle performance in normally active older men, combined with examination of the molecular and metabolic mechanisms regulating physiological responses.

Inclusion Criteria:

• Male
• Age between 65-75 years
• Body mass index between 19-29
• No active cardiovascular or metabolic disease
• No active respiratory disease
• No current musculoskeletal injuries
• A sedentary lifestyle (i.e. does not engage in strenuous, planned physical activity)
• The ability to give informed consent

Exclusion Criteria:

• Currently taking a statin drug or NSAIDs
• Have a current peptic ulcer
• Have any renal impairment
• Have a known hypersensitivity to Acipimox