Universität zu Köln

Tosetti, Bettina, Brodesser, Susanne, Brunn, Anna, Deckert, Martina, Blueher, Matthias, Doehner, Wolfram, Anker, Stefan D., Wenzel, Daniela ORCID: 0000-0003-1100-6363, Fleischmann, Bernd, Pongratz, Carola, Peters, Franziska, Utermoehlen, Olaf and Kroenke, Martin (2020). A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle. Aging Cell, 19 (1). HOBOKEN: WILEY. ISSN 1474-9726

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Abstract

Loss of skeletal muscle mass is one of the most widespread and deleterious processes in aging humans. However, the mechanistic metabolic principles remain poorly understood. In the framework of a multi-organ investigation of age-associated changes of ceramide species, a unique and distinctive change pattern of C-16:0 and C-18:0 ceramide species was detected in aged skeletal muscle. Consistently, the expression of CerS1 and CerS5 mRNA, encoding the ceramide synthases (CerS) with substrate preference for C-16:0 and C-18:0 acyl chains, respectively, was down-regulated in skeletal muscle of aged mice. Similarly, an age-dependent decline of both CerS1 and CerS5 mRNA expression was observed in skeletal muscle biopsies of humans. Moreover, CerS1 and CerS5 mRNA expression was also reduced in muscle biopsies from patients in advanced stage of chronic heart failure (CHF) suffering from muscle wasting and frailty. The possible impact of CerS1 and CerS5 on muscle function was addressed by reversed genetic analysis using CerS1(Delta/Delta) and CerS5(Delta/Delta) knockout mice. Skeletal muscle from mice deficient of either CerS1 or CerS5 showed reduced caliber sizes of both slow (type 1) and fast (type 2) muscle fibers, fiber grouping, and fiber switch to type 1 fibers. Moreover, CerS1- and CerS5-deficient mice exhibited reduced twitch and tetanus forces of musculus extensor digitorum longus. The findings of this study link CerS1 and CerS5 to histopathological changes and functional impairment of skeletal muscle in mice that might also play a functional role for the aging skeletal muscle and for age-related muscle wasting disorders in humans.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Tosetti, Bettina UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Brunn, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Deckert, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Blueher, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Doehner, Wolfram UNSPECIFIED UNSPECIFIED UNSPECIFIED Anker, Stefan D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wenzel, Daniela UNSPECIFIED orcid.org/0000-0003-1100-6363 UNSPECIFIED Fleischmann, Bernd UNSPECIFIED UNSPECIFIED UNSPECIFIED Pongratz, Carola UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Utermoehlen, Olaf UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroenke, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128138
DOI:	10.1111/acel.13049
Journal or Publication Title:	Aging Cell
Volume:	19
Number:	1
Date:	2020
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1474-9726
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SPHINGOLIPID METABOLISM; MASS; MUTATIONS; FEATURES; REVEALS; GENE Multiple languages Cell Biology; Geriatrics & Gerontology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12813