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Effects of Ageing and Physical Activity on Regulation of Muscle Contraction
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
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.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 369
Keyword [en]
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
Identifiers
URN: urn:nbn:se:uu:diva-9198ISBN: 978-91-554-7258-0 (print)OAI: oai:DiVA.org:uu-9198DiVA: diva2:172365
Public defence
2008-09-19, Hedstrandssalen, Akademiska Sjukhuset, Ingång 70, Entréplan, Uppsala, 09:15
Opponent
Supervisors
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2012-11-13Bibliographically approved
List of papers
1. Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
Open this publication in new window or tab >>Effects of ageing and gender on contractile properties in human skeletal muscle and single fibres
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2007 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 190, no 3, 229-241 p.Article in journal (Refereed) Published
Abstract [en]

Aim: The objective of this study is to improve our understanding of the mechanisms underlying the ageing- and gender-related muscle weakness.

Methods: Ageing- and gender-related differences in regulation of muscle contraction have been studied in knee-extensor muscles at the whole muscle and single muscle fibre levels in young and old sedentary men and women. In vivo knee-extensor muscle function was measured at slow (30° s−1) and faster (180 ° s−1) speeds of movement. Maximum velocity of unloaded shortening (V0) and maximum force normalized to cross-sectional area (CSA) [specific tension (ST)] were measured in single 'skinned' skeletal muscle fibre segments.

Results: Significant ageing- and gender-related differences were observed in muscle torque. A 33–55% ageing-related decline (P < 0.001) in maximum torque was observed irrespective of gender. At the single muscle fibre level, the ageing-related decline in knee-extensor muscle function was accompanied by a 20–28% decline in ST in muscle fibres expressing the type I MyHC isoform in both men and women, and a 29% decline in type IIa muscle fibre CSA, but the decreased fast-twitch fibre size was restricted to the men. Furthermore, in both men and women, V0 decreased in muscle cells expressing the type I and IIa MyHC isoforms.

Conclusion: The present results provide evidence of specific ageing- and gender-related differences in regulation of muscle contraction at the cellular level. It is suggested that these cellular changes have a significant impact on muscle function and the ageing-related motor handicap.

Keyword
maximum velocity of unloaded shortening, muscle mass, skinned fibres, slack test, specific tension, torque-velocity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97417 (URN)10.1111/j.1748-1716.2007.01699.x (DOI)000247318600006 ()
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2011-02-05Bibliographically approved
2. Aging, muscle fiber type, and contractile function in sprint-trained athletes
Open this publication in new window or tab >>Aging, muscle fiber type, and contractile function in sprint-trained athletes
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2006 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 101, no 3, 906-917 p.Article in journal (Refereed) Published
Abstract [en]

Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V-o) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V-o of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V-o of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V-o of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.

Keyword
exercise, myosin heavy chain, single-fiber contractile properties, muscle strength
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97418 (URN)10.1152/japplphysiol.00299.2006 (DOI)000240124100031 ()16690791 (PubMedID)
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2011-06-21Bibliographically approved
3. Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
Open this publication in new window or tab >>Effects of combined strength and sprint training on regulation of muscle contraction at the whole-muscle and single fibre levels in elite master sprinters
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2008 (English)In: Acta Physiologica, ISSN 1748-1708, Vol. 193, no 3, 275-289 p.Article in journal (Refereed) Published
Abstract [en]

AIM: This study aims at examining the effects of progressive strength and sprint training on regulation of muscle contraction at the whole-muscle and single-fibre levels in older sprint-trained athletes. METHODS: Eleven men (52-78 years) were randomized to a training (EX, n = 7) or control (CTRL, n = 4) group. EX participated in a 20-week programme that combined sprint training with heavy and explosive strength exercises, while CTRL maintained their usual run-based training schedules. RESULTS: EX improved maximal isometric and dynamic leg strength, explosive jump performance and force production in running. Specific tension and maximum shortening velocity of single fibres from the vastus lateralis were not altered in EX or CTRL. Fibre type and myosin heavy chain isoform distributions remained unchanged in the two groups. There was a general increase in fibre areas in EX, but this was significant only in IIa fibres. The 10% increase in squat jump in EX was accompanied by a 9% increase in the integrated EMG (iEMG) of the leg extensors but the 21-40% increases in isometric and dynamic strength were not paralleled by changes in iEMG. CONCLUSION: Adding strength training stimulus to the training programme improved maximal, explosive and sport-specific force production in elite master sprinters. These improvements were primarily related to hypertrophic muscular adaptations.

Keyword
ageing, fibre types, hypertrophy, master athletes, neural activity, skinned fibres
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97419 (URN)10.1111/j.1748-1716.2008.01843.x (DOI)000256442100010 ()18284658 (PubMedID)
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2009-11-03Bibliographically approved
4. Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
Open this publication in new window or tab >>Effects of ageing and gender on the spatial organisation of nuclei in single human skeletal muscle cells
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Manuscript (Other academic)
Identifiers
urn:nbn:se:uu:diva-97420 (URN)
Available from: 2008-08-29 Created: 2008-08-29 Last updated: 2010-01-13Bibliographically approved

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