Long Noncoding RNA Lnc-mar Contributes to the Maintenance of Skeletal Muscle Mass and Strength during Aging (abstract)

Sarcopenia, age-related loss of skeletal muscle mass and strength, is associated with serious health consequences. However, there is still no clinically established therapy for sarcopenia to date. We previously identified one long noncoding RNA (lncRNA), lnc-mar, which was the most down-regulated lncRNA in atrophied muscle of hindlimb suspension (HLS) mice. Further in vitro and in vivo study demonstrated that the decreased expression level of lnc-mar closely associated with the reduction of myogenesis during mechanical unloading. The overexpression of lnc-mar in skeletal muscle prevented the muscle atrophy development in HLS mice. Here, we investigated the role of lnc-mar in sarcopenia development during aging. The expression of lnc-mar was significantly down-regulated in skeletal muscle of aged mice, which was associated with decreased expression of MyoD and low muscle mass. Mechanistically, lnc-mar promoted myogenic differentiation by functioning as a miR-762 sponge to regulate the core myogenic regulator MyoD in vitro. The enforced expression of lnc-mar relieved the decreases in MyoD protein and muscle mass in miR-762 knock-in mice. Therapeutically, the enforced expression of lnc-mar promoted the MyoD expression, improved the myogenic differentiation of myoblasts in vitro, attenuated the decreases in muscle histomorphometric (i.e., muscle mass and muscle fiber CSA) and functional (i.e., muscle strength) parameters in aging mice. These findings suggest that lnc-mar functions as an anabolic regulator in skeletal muscle and contributes to the maintenance of muscle mass and strength during aging. It could be a potential therapeutic target to counteract sarcopenia development during aging.