Attenuation of Muscle Loss and Maintained Growth Response in Aged Mice with a Null Deletion of Muscle Ring Finger 1 (MuRF1)

Abstract

During aging progressive declines occur in both the force producing capacity and the oxidative capacity of skeletal muscle. Further, aging is associated with a resistance to muscle growth in response to increased loading. Muscle Ring Finger 1 (MuRF1), a muscle specific ubiquitin ligase, is expressed at low levels in resting muscle, but up-regulated under a variety of atrophy-inducing conditions including denervation, disuse, and possibly aging. Deletion of MuRF1 (KO) attenuates the loss of muscle mass during atrophy; however, its role in aging has not been investigated. Thus, the objective of this study was to examine the metabolic, contractile and growth properties of wild type (WT) and MuRF1 KO mice at 6, 18, and 24 months of age. At 24 months WT, but not KO, mice had significantly lower gastrocnemius mass. Morphological analyses revealed significant decreases in fiber cross sectional area and capillary to fiber ratio in 24 month WT, but not KO mice. Muscle growth was examined following 14-days of functional overload of the plantaris in young and old WT and KO mice. Load-induced growth was similar in young WT and KO mice. Old KO mice maintained the growth response observed in young mice, whereas load-induced growth was significantly less in old WT mice. These data suggest that MuRF1 may play an important role in age-related loss of muscle mass and anabolic resistance. Supported by NIH RO1DK75801 and T32HL086350.