Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, KY, USA; Center for Muscle Biology, University of Kentucky, Lexington, KY, USA.
Department of Molecular Medicine, Scripps Research, La Jolla, CA, USA.
Exp Gerontol. 2021 Apr;146:111214. doi: 10.1016/j.exger.2020.111214. Epub 2020 Dec 30.
RNA binding protein motif 3 (RBM3) is an RNA-binding and cold shock protein that protects myoblasts and promotes skeletal muscle hypertrophy by enhancing mRNA stability and translation. Muscle size is decreased during aging; however, it is typically delayed in models of extended lifespan such as the long-lived Ames Dwarf (df/df) mice and calorie restricted (CR) animals compared to age-matched controls. In light of the protective and anabolic effects of RBM3 in muscle, we hypothesized that RBM3 expression is higher in long-lived animal models. Young and old df/df mice, and adult and old UM-HET3 CR mice were used to test this hypothesis. Gastrocnemius muscles were harvested and protein was isolated for RBM3 protein measurements. CR induced a 1.7 and 1.3-fold elevation in RBM3 protein abundance compared to adult and old male mice fed ad libitum (AL) diets, respectively; this effect was shared between males and females. Ames dwarfism induced a 4.6 and 2.7-fold elevation in RBM3 protein abundance in young and old df/df mice compared to normal control littermates, respectively. In contrast, there was an age-associated decrease in cold-inducible RNA-binding protein (CIRP), suggesting these effects are specific for RBM3. Lastly, there was an age-associated increase in RNA degradation marker decapping enzyme 2 (DCP2) in UM-HET3 mice that was mitigated by CR. These results show that muscle RBM3 expression is correlated with extended lifespan in both df/df and CR animals. Identifying how RBM3 exerts protective effects in muscle may yield new insights into healthy aging of skeletal muscle.
RNA 结合蛋白基序 3（RBM3）是一种 RNA 结合蛋白和冷休克蛋白，可通过增强 mRNA 稳定性和翻译来保护成肌细胞并促进骨骼肌肥大。随着年龄的增长，肌肉会变小；然而，与年龄匹配的对照相比，在延长寿命的模型中，如长寿的 Ames 矮（df/df）小鼠和热量限制（CR）动物中，肌肉大小的减少通常会延迟。鉴于 RBM3 在肌肉中的保护和合成代谢作用，我们假设 RBM3 在长寿动物模型中的表达更高。使用年轻和年老的 df/df 小鼠以及成年和年老的 UM-HET3 CR 小鼠来测试这一假设。采集比目鱼肌并分离蛋白质以测量 RBM3 蛋白。与自由进食（AL）饮食的成年和老年雄性小鼠相比，CR 分别使 RBM3 蛋白丰度增加了 1.7 倍和 1.3 倍；这种作用在雄性和雌性之间是共享的。与正常对照同窝仔相比，Ames 矮小症使年轻和年老的 df/df 小鼠的 RBM3 蛋白丰度分别增加了 4.6 倍和 2.7 倍。相比之下，在 UM-HET3 小鼠中，冷诱导 RNA 结合蛋白（CIRP）随年龄的增长而减少，表明这些作用是 RBM3 特异性的。最后，在 UM-HET3 小鼠中，与年龄相关的 RNA 降解标记物脱帽酶 2（DCP2）增加，但 CR 可减轻这种增加。这些结果表明，RBM3 在 df/df 和 CR 动物中的肌肉表达与延长寿命相关。确定 RBM3 如何在肌肉中发挥保护作用，可能为骨骼肌的健康衰老提供新的见解。
