Fig. 8.

It is envisaged that small episodes of denervation, such as loss of single terminal axons occur frequently throughout life and that this is rapidly repaired by axonal sprouting and outgrowth. Each cycle of denervation and re-innervation leads to a transient increase in mitochondrial peroxide generation in the denervated and neighbouring muscle fibers which cause minor oxidative damage and induction of adaptative responses to prevent further oxidative damage. The repetition of this process many times over a lifetime eventually leads to the cumulative increase in oxidative damage seen in muscle tissue of older animals and man, and also to a cumulative adaptive increase in regulatory proteins designed to prevent oxidative damage, including those in the cytosol that cause a greater reduction in the redox status of critical cysteines (as in Fig. 7B). These changes thus lead to the attenuated redox responses to exercise seen in muscle from old mice and humans which compromises the ability to maintain muscle mass and function in old age.