Abstract

2024 R Jean Banister Prize Lecture, from the Physiological Society.

Skeletal muscle is the largest organ in the body playing vital roles in locomotion and metabolism. As we age, we progressively lose muscle mass and strength, which increases the risk of frailty-related falls, morbidity and mortality. Ageing muscle also displays an impaired capacity to fully adapt to current countermeasures e.g., resistance exercise (RE) training (RET). Despite the socioeconomic significance of muscle decline, the underlying mechanisms remain to be fully defined, and fully effective countermeasures remain elusive. Using biologicallydriven transcriptional meta-analysis, we identified altered mitochondrial networks to be associated with muscle atrophy, and extracellular matrix, immune and inflammatory networks to be associated with impaired adaptation to RET in older muscle. To rejuvenate the mitochondria, we trialled the effects of a nicotinamide adenine dinucleotide (NAD+) precursor, nicotinic acid, in older adults. We found that two weeks supplementation altered carbohydrate, citric acid cycle and electron transport genes, and upregulated NAD + related pathways, indicating metabolic programming. Our results so far have identified molecular candidates for understanding and treating age-related muscle decline.