During postnatal development and continuing through the aging process, there are changes in the dynamic metabolic processes that maintain the structural and functional properties of axons. For exampIe, the rate of slow transport decreases during maturation and aging. Our studies are aimed at elucidating the cell biological mechanisms that produce these changes in aging axons. To achieve this goal, we are examining the factors that affect the translocation of cytoskeletal polymers in axons. Our premise is that the slow transport mechanisms operate by producing polymer sliding movements. To directly examine polymer sliding in axons we have developed a new experimental method for slowly stretching axoplasm at rates approaching those of slow transport. With this method the resistance of polymers to sliding can be measured directly. In addition, we are using the electron microscope to study the interactions between axonal neurofilaments in axons with different slow transport rates. If these interactions are imporant determinants of transport rate, then the organization of the neurofilaments should correlate with the rate of transport. Cytoskeletal and membranous elements are transported to the axon terminal and they provide the materials for axon terminal structures. The amount of material available at the terminal is determined by the rate of supply to the terminal and removal from the terminal. In aging terminals, the balance between supply and removal changes and in some neurons excess membranous and cytoskeletal elements accumulate at the terminals. This excess may be produced by a decrease in the rate of removal from the axon terminal. To examine this possibility, we are using radioisotopic methods, to determine whether the rate of removal changes during aging. These studies will contribute to understanding the mechanisms that normally operate to remove excess materials from axon terminals and to understanding how changes in these mechanisms contribute to changes in the properties of axon terminals during aging.
