Influence of aging and long-term unloading on the structure and function of human skeletal muscle.

Understanding the quantitative and qualitative changes in skeletal muscle that control changes in function is crucial in the development of countermeasures to the loss of skeletal muscle function observed with real and simulated microgravity exposure (i.e., unloading) and with aging in humans. Qualitative changes that could influence the force and power producing properties of skeletal muscle are changes in the distribution of the 3 isoforms of the main motor protein myosin heavy chain (MHC), as well as the abundance of MHC, actin (the other main contractile protein), and the force distributing the connective tissue network. Numerous studies have examined quantitative and qualitative changes in skeletal muscle, from the whole muscle to the single myofiber from individuals undergoing real and simulated space flight for a few weeks to several months, as well as from aging men and women. When considering the relative content of the main functional and structural elements (i.e., myosin, actin, collagen), it appears that human muscle appropriately scales changes in size of 10%-40% induced over a relatively short time period (1-3 months) and over the lifespan (in humans 20 to 90+ years old). The main qualitative change with unloading and aging is a redistribution of the 3 MHC isoforms, which have vastly different contractile characteristics. It is now known that the response of skeletal muscle to unloading is muscle and gender specific. In summary, changes in muscle mass (quantity) combined with the alterations in MHC distribution (quality) are the primary determinants of changes in muscle function with unloading and aging. These parameters are the key components of muscle that should be targeted with countermeasures for conditions related to muscle loss, along with considerations for muscle- and gender-specific responses.