Meyer, Angelika, Ibebunjo, Chikwendu, Solovyeva, Elizaveta, Utzinger, Stephan, Eash, John, Dunbar, Andrew W., Demirci, Sabrina, Naumann, Ulrike, Zhang, Yunyu, Serluca, Fabrizio, Oberhauser, Berndt, Black, Frederique, Rausch, Martin, Trifilieff, Estelle, Hoersch, Sebastian and Trendelenburg, Anne-Ulrike (2021) New insights into molecular changes in skeletal muscle aging and disease: Differential alternative splicing and senescence. Mechanisms of Ageing and Development, 197 (111510). pp. 1-13. ISSN 18726216

Abstract

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.

Item Type:	Article
Keywords:	Cellular senescence Differential alternative splicing Laser capture microdissection Myotonic dystrophy type 1 Sarcopenia
Date Deposited:	08 Aug 2021 00:45
Last Modified:	08 Aug 2021 00:45
URI:	https://oak.novartis.com/id/eprint/44370