Universität zu Köln

Diermeier, Stefanie, Buttgereit, Andreas, Schuermann, Sebastian, Winter, Lilli ORCID: 0000-0002-6368-1160, Xu, Hongyang, Murphy, Robyn M., Clemen, Christoph S., Schroeder, Rolf and Friedrich, Oliver ORCID: 0000-0003-2238-2049 (2017). Preaged remodeling of myofibrillar cytoarchitecture in skeletal muscle expressing R349P mutant desmin. Neurobiol. Aging, 58. S. 77 - 88. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1558-1497

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Abstract

The majority of hereditary and acquired myopathies are clinically characterized by progressive muscle weakness. We hypothesized that ongoing derangement of skeletal muscle cytoarchitecture at the single fiber level may precede and be responsible for the progressive muscle weakness. Here, we analyzed the effects of aging in wild-type (wt) and heterozygous (het) and homozygous (hom) R349P desmin knock-in mice. The latter harbor the ortholog of the most frequently encountered human R350P desmin missense mutation. We quantitatively analyzed the subcellular cytoarchitecture of fast- and slow-twitch muscles from young, intermediate, and aged wt as well as desminopathy mice. We recorded multiphoton second harmonic generation and nuclear fluorescence signals in single muscle fibers to compare aging-related effects in all genotypes. The analysis of wt mice revealed that the myofibrillar cytoarchitecture remained stable with aging in fast-twitch muscles, whereas slow-twitch muscle fibers displayed structural derangements during aging. In contrast, the myofibrillar cytoarchitecture and nuclear density were severely compromised in fast- and slow-twitch muscle fibers of hom R349P desmin mice at all ages. Het mice only showed a clear degradation in their fiber structure in fast-twitch muscles from the adult to the presenescent age bin. Our study documents distinct signs of normal and R349P mutant desmin-related remodeling of the 3D myofibrillar architecture during aging, which provides a structural basis for the progressive muscle weakness. (C) 2017 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Diermeier, Stefanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Buttgereit, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schuermann, Sebastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Winter, Lilli UNSPECIFIED orcid.org/0000-0002-6368-1160 UNSPECIFIED Xu, Hongyang UNSPECIFIED UNSPECIFIED UNSPECIFIED Murphy, Robyn M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Clemen, Christoph S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeder, Rolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Friedrich, Oliver UNSPECIFIED orcid.org/0000-0003-2238-2049 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217248
DOI:	10.1016/j.neurobiolaging.2017.06.001
Journal or Publication Title:	Neurobiol. Aging
Volume:	58
Page Range:	S. 77 - 88
Date:	2017
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1558-1497
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MDX MICE; AGE; MOUSE; FIBERS; REGENERATION; DISEASE; DESMINOPATHIES; MECHANISMS; MORPHOLOGY; DYSTROPHY Multiple languages Geriatrics & Gerontology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21724