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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

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...

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Autores principales: Tosetti, Bettina, Brodesser, Susanne, Brunn, Anna, Deckert, Martina, Blüher, Matthias, Doehner, Wolfram, Anker, Stefan D., Wenzel, Daniela, Fleischmann, Bernd, Pongratz, Carola, Peters, Franziska, Utermöhlen, Olaf, Krönke, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974707/
https://www.ncbi.nlm.nih.gov/pubmed/31692231
http://dx.doi.org/10.1111/acel.13049
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author Tosetti, Bettina
Brodesser, Susanne
Brunn, Anna
Deckert, Martina
Blüher, Matthias
Doehner, Wolfram
Anker, Stefan D.
Wenzel, Daniela
Fleischmann, Bernd
Pongratz, Carola
Peters, Franziska
Utermöhlen, Olaf
Krönke, Martin
author_facet Tosetti, Bettina
Brodesser, Susanne
Brunn, Anna
Deckert, Martina
Blüher, Matthias
Doehner, Wolfram
Anker, Stefan D.
Wenzel, Daniela
Fleischmann, Bernd
Pongratz, Carola
Peters, Franziska
Utermöhlen, Olaf
Krönke, Martin
author_sort Tosetti, Bettina
collection PubMed
description 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 (Δ/Δ) and CerS5 (Δ/Δ) 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.
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spelling pubmed-69747072020-01-28 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 Tosetti, Bettina Brodesser, Susanne Brunn, Anna Deckert, Martina Blüher, Matthias Doehner, Wolfram Anker, Stefan D. Wenzel, Daniela Fleischmann, Bernd Pongratz, Carola Peters, Franziska Utermöhlen, Olaf Krönke, Martin Aging Cell Original Articles 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 (Δ/Δ) and CerS5 (Δ/Δ) 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. John Wiley and Sons Inc. 2019-11-06 2020-01 /pmc/articles/PMC6974707/ /pubmed/31692231 http://dx.doi.org/10.1111/acel.13049 Text en © 2019 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Tosetti, Bettina
Brodesser, Susanne
Brunn, Anna
Deckert, Martina
Blüher, Matthias
Doehner, Wolfram
Anker, Stefan D.
Wenzel, Daniela
Fleischmann, Bernd
Pongratz, Carola
Peters, Franziska
Utermöhlen, Olaf
Krönke, Martin
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6974707/
https://www.ncbi.nlm.nih.gov/pubmed/31692231
http://dx.doi.org/10.1111/acel.13049
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