Mechanism of eccentric training augmentation of muscle adaptation in humans and the potential negative impact of non-steroidal anti-inflammatory drugs

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This project is aimed at elucidating how long-term physical training involving both lengthening and shortening muscle contractions increases muscle size and strength in humans above shortening contractions alone, and whether chronic ingestion of non-steroidal anti-inflammatory drugs impairs this process. In collaboration with UK Sport, the BBSRC has made funding available for research applications that will specifically utilise 'fundamental bioscience to provide new insights into the stress and adaptation required to maximise physical potential', and by doing so will 'address many of the major challenges facing high performance sport in the UK through athletic training and performance.' This project meets this remit on two fronts: (i) Although we know that resistance training which involves a combination of lengthening and shortening muscle contractions results in greater muscle mass and strength gains than training involving only shortening contractions, and is used widely by athletes to maximise performance gains, our understanding of the mechanisms by which this is achieved is at a rudimentary level. Furthermore, we know nothing about the time-course of muscle performance gains and physiological changes that occur during this type of training. It is known that muscle inflammation is greater after a single bout of lengthening contractions compared to shortening contractions, which may be important. Therefore we aim to use a basic bioscience approach to examine whether augmented muscle growth factor expression and muscle specific stem cell proliferation, that we believe occur secondary to exercise induced muscle inflammation, is the mechanism by which a sustained period of training involving combined lengthening and shortening contractions augments muscle mass and strength gains over training involving only shortening contractions. This aspect of the project will provide detailed, broad-based mechanistic insight of how resistance exercise training results in positive muscle adaptation and functional gains in humans. In addition to being of importance to our fundamental understanding of physiological adaptation to exercise stress, and thereby maximising athletic performance, it has wider relevance to our understanding of how we might minimise the loss of muscle mass that accompanies ageing (sarcopaenia). (ii) Non-steroidal anti-inflammatory drugs (NSAID's) are widely used in top level sport as a prophylactic agent to seemingly minimise pain and injury and maximise training adaptation, but given the emerging role of inflammation in stimulating muscle growth responses (including muscle stem cell activation), there is a distinct possibility that chronic prophylactic use of NSAID's may impair muscle adaptation to resistance training, thereby blunting athlete performance development (in addition to being unsafe). The present project will address a major challenge facing high performance sport in the UK by determining whether NSAID ingestion during a programme of resistance training can blunt training induced increases in muscle function (by attenuating muscle inflammation, muscle growth factor responses and stem cell activation and proliferation). Clearly therefore this project will provide valuable, novel information concerning the potential negative effect of prophylactic NSAID use by athletes, thereby fulfilling the requirement of UK Sport of linking fundamental biological research to high performance sport.