-Agonist administration increases sarcoplasmic reticulum Ca 2ϩ -ATPase activity in aged rat skeletal muscle. Am J Physiol Endocrinol Metab 288: E526 -E533, 2005. First published October 12, 2004 doi:10.1152/ ajpendo.00399.2004.-Aging is associated with a slowing of skeletal muscle contractile properties, including a decreased rate of relaxation. In rats, the age-related decrease in the maximal rate of relaxation is reversed after 4-wk administration with the  2-adrenoceptor agonist ( 2-agonist) fenoterol. Given the critical role of the sarcoplasmic reticulum (SR) in regulating intracellular Ca 2ϩ transients and ultimately the time course of muscle contraction and relaxation, we tested the hypothesis that the mechanisms of action of fenoterol are mediated by alterations in SR proteins. Sarcoendoplasmic reticulum Ca 2ϩ -ATPase (SERCA) kinetic properties were assessed in muscle homogenates and enriched SR membranes isolated from the red (RG) and white (WG) portions of the gastrocnemius muscle in adult (16 mo) and aged (28 mo) F344 rats that had been administered fenoterol for 4 wk (1.4 mg/kg/day ip, in saline) or vehicle only. Aging was associated with a 29% decrease in the maximal activity (V max) of SERCA in the RG but not in the WG muscles. Fenoterol treatment increased the V max of SERCA and SERCA1 protein levels in RG and WG. In the RG, fenoterol administration reversed an age-related selective nitration of the SERCA2a isoform. Our findings demonstrate that the mechanisms underlying age-related changes in contractile properties are fiber type dependent, whereas the effects of fenoterol administration are independent of age and fiber type.aging; calcium; -adrenoceptor; contractility SARCOPENIA, THE PROGRESSIVE LOSS of skeletal muscle mass with advancing age, is associated with a decline in muscle strength that leads to a loss of functional independence and a reduced quality of life (17). Aging is also associated with a slowing of the time course of skeletal muscle contraction and relaxation (15). These changes can reduce the accuracy and precision of movements, impair the ability to perform simple tasks, and increase the risk of sudden falls and related injuries. Ideally, therapies to prevent or reverse the age-related changes in skeletal muscle should also target the slowing of contraction and relaxation, in addition to preserving or increasing muscle mass and strength.Neurogenic factors, such as motor unit remodeling and denervation, have been implicated in the age-related changes to skeletal muscle (11). However, myogenic factors are also involved, since the slowing of contraction and relaxation occurs before the onset of muscle wasting (18,20,21). Intrinsic changes to skeletal muscle fibers appear to be involved in the deterioration of function with age. Specifically, age-related changes in the proteins regulating Ca 2ϩ handling during excitation-contraction coupling and relaxation have been described (15).Relaxation of skeletal muscle is thought to involve at least three processes: dissociation of Ca 2...