How do muscles become weak from disuse?

Lost sarcomeres. The loss of muscle from a casted limb is very familiar, but little is known about the mechanism. The muscle cells burn their own contractile units (sarcomeres) if they are not exercised as they are accustomed. The molecular biology remains largely obscure; the newly-discovered molecule myostatin is one of the factors, and myostatin-deficient individuals have less atrophy of disuse.