Progressive loss of muscle mass and function due to muscle fiber atrophy and loss in the elderly and chronically ill is now defined as sarcopenia. It is a major contributor to loss of independence, disability, need of long-term care as well as overall mortality. Sarcopenia is a heterogenous disease and underlying mechanisms are not completely understood. Here, we newly identified and used Tmem158, alongside Cdkn1a, as relevant senescence and denervation markers (SDMs), associated with muscle fiber atrophy. Subsequent application of laser capture microdissection (LCM) and RNA analyses revealed age- and disease-associated differences in gene expression and alternative splicing patterns in a rodent sarcopenia model. Of note, genes exhibiting such differential alternative splicing (DAS) are mainly involved in the contractile function of the muscle. Many of these splicing events are also found in a mouse model for myotonic dystrophy type 1 (DM1), underscoring the premature aging phenotype of this disease. We propose to add differential alternative splicing to the hallmarks of aging.

由于老年人和慢性病患者的肌纤维萎缩和丧失导致的肌肉质量和功能的进行性丧失现在被定义为肌肉减少症。它是导致丧失独立性、残疾、需要长期护理以及总体死亡率的主要原因。肌肉减少症是一种异源性疾病，其潜在机制尚不完全清楚。在这里，我们新发现并使用 Tmem158 以及 Cdkn1a 作为与肌肉纤维萎缩相关的相关衰老和去神经标记 (SDM)。随后应用激光捕获显微切割 (LCM) 和 RNA 分析揭示了啮齿动物肌肉减少症模型中基因表达和可变剪接模式的年龄和疾病相关差异。值得注意的是，表现出这种差异选择性剪接 (DAS) 的基因主要涉及肌肉的收缩功能。在 1 型强直性肌营养不良 (DM1) 的小鼠模型中也发现了许多这些剪接事件，强调了这种疾病的过早衰老表型。我们建议将差异选择性剪接添加到衰老的标志中。