Examining the impact of inactivity and diet on muscle health with age in C. elegans

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Intuitively we know that lack of physical activity makes us feel both mentally and physically worse. We also appreciate that as we get older we become less active and less healthy. Surprisingly, the World Health Organization has found that inactivity does indeed cause poorer health and that, in fact, it is the fourth leading cause of death worldwide. Despite the importance of inactivity on poor health, the majority of research on how inactivity causes poor health has been conducted in astronauts (e.g. less than 900 individuals worldwide since the 1960s!). Currently allot of research is conducted on the impact of activity on health with the assumption that the mechanisms that promote health in response to activity are the same ones that promote lack of health with inactivity. However, loss of muscle in response to spaceflight or confinement to bed is rapid and large (>7% loss in 7 days, a dramatic decrease in 1 week) whereas increase in muscle in response to exercise is much slower (nobody gets fit in just 1 week at the sports centre). Thus, research into how inactivity causes poor health is needed and needed quickly. In order to gain this knowledge faster, we propose to study how inactivity causes poor health in a tiny worm and later to test if the same mechanisms act in people. This may seem far fetched but we have already shown that the muscles of this tiny worm respond to spaceflight much the same way astronauts muscles do, with many changes in the molecules that cause much to be strong and make energy declining rapidly in both the worm and in astronauts. Our past spaceflight work has suggested that decreased signal from nerve to muscle occurs in spaceflown worms and similar changes are seen in people confined to bed. Therefore we will systematically decrease signal from nerve to muscle in worms and determine the impact upon health and particularly muscle health decline with age. We will specifically ask: i) Does it matter when you are inactive (e.g. child vs. adult) in terms of the impact on health and muscle health decline with age; ii) Do repeated episodes of inactivity during adulthood (e.g. working at a desk, hospitalization, etc) have additive negative impacts on health and muscle decline with age; and iii) Can diet which produces increased health (e.g. longer life) protect against the impact of inactivity? The results of these experiments will allow us to begin to understand the molecules that control these processes and, in the future, possibly design new drugs. Equally importantly, the results from these experiments will provide a framework for testing if the findings from the worm also hold true in people but in a faster and cheaper way than starting with studying people (much as we used animals to prove spaceflight was safe before sending astronauts).