The regulation of muscle stem cell migration in ageing

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The increase in the longevity of individuals in Western societies will present considerable challenges to the healthcare and economic systems of developed countries as they care for people whose body functions undergo age-related deterioration. Old age is associated with a progressive loss of skeletal muscle mass, a process called sarcopenia. Aged related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility, increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle contains stem cells that in the young are able to maintain mass. Aged muscle contains stem cells but these are not able to maintain mass. We have recently shown that aged muscle stem cells move considerably slower than young stem cells and postulate that the ability to migrate is crucial in the repair process. Importantly we found that Nitric Oxide, a powerful cell signalling molecule, enabled old muscle cells stem to move at speeds of young cells. In this investigation we aim to determine when mice develop deficits in migration speeds and how this correlates with changes in Nitric Oxide levels in muscle. We will then optimise the means of increasing Nitric Oxide levels in muscle and relate these to changes in muscle stem cell migration speeds. Finally we will use data generated from all previous section of this package to develop a regime that increases Nitric Oxide in aged muscle and determine whether it improves the muscle repair process.We aim to show that increasing muscle stem cell migration using Nitric Oxide results in an enhanced rate of repair. Significantly, a number of drugs that increase Nitric Oxide levels have already been approved for use in humans. Therefore it is possible that results of our study could be rapidly translated into regimes to prevent age related muscle loss in humans.