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Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience.
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Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-97420OAI: oai:DiVA.org:uu-97420DiVA: diva2:172364
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Effects of Ageing and Physical Activity on Regulation of Muscle Contraction
Open this publication in new window or tab >>Effects of Ageing and Physical Activity on Regulation of Muscle Contraction
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The aims of this study were to investigate the mechanisms underlying (1) the ageing-related motor handicap at the whole muscle, cellular, contractile protein and myonuclear levels; and (2) ageing-related differences in muscle adaptability.

In vivo muscles function was studied in the knee extensors. Decreases were observed in isokinetic and isometric torque outputs in old age in the sedentary men and women and elite master sprinters. A 20-week long specific sprint and resistance training successfully improved the maximal isometric force and rate of force development in a subgroup of master sprinters.

In vitro measurements were performed in muscle biopsies from the vastus lateralis muscle. Immunocytochemical and contractile measurements in single membrane permeabilized muscle fibres demonstrated ageing- and gender-related changes at the myofibrillar level. In sedentary subjects, data showed a preferential decrease in the size of muscle fibres expressing type IIa MyHC in men, lower force generating capacity in muscle fibres expressing the type I MyHC isoform in both men and women and lower maximum velocity of unloaded shortening (V0) in fibres expressing types I and IIa MyHC isoforms in both men and women. The master sprinters also experienced the typical ageing-related reduction in the size of fast-twitch fibres, a shift toward a slower MyHC isoform profile and a lower V0 of type I MyHC fibres, which played a role in the decline in explosive force production capacity. The fast-twitch fibre area increased after the resistance training period. A model combining single muscle fibre confocal microscopy with a novel algorithm for 3D imaging of myonuclei in single muscle fibre segments was introduced to study the spatial organisation of myonuclei and the size of individual myonuclear domains (MNDs). Significant changes in the MND size variability and myonuclear organization were observed in old age, irrespective gender and fibre type. Those changes may influence the local quantity of specific proteins per muscle fibre volume by decreased and/or local cooperativity of myonuclei in a gender and muscle fibre specific manner.

In conclusion, the ageing-related impairments in in vivo muscle function were related to significant changes in morphology, contractile protein expression and regulation at the muscle fibre level. It is suggested that the altered myonuclear organisation observed in old age impacts on muscle fibre protein synthesis and degradation with consequences for the ageing-related changes in skeletal muscle structure and function. However, the improved muscle function in response to a 20-week intense physical training regime in highly motivated physically active old subjects demonstrates that all ageing-related in muscle function are not immutable.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 77 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 369
ageing, sarcopenia, sprint training, progressive resistance training, in vivo function, isokinetic dynamometer, in vitro function, single permeabilised fibre, myonuclear domain, confocal microscopy
National Category
Clinical Science
urn:nbn:se:uu:diva-9198 (URN)978-91-554-7258-0 (ISBN)
Public defence
2008-09-19, Hedstrandssalen, Akademiska Sjukhuset, Ingång 70, Entréplan, Uppsala, 09:15
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2012-11-13Bibliographically approved

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