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Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. (Professor Lars Larsson group)
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Centrum för bildanalys. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Datoriserad bildanalys.
Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Centrum för bildanalys. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Matematisk-datavetenskapliga sektionen, Institutionen för informationsteknologi, Datoriserad bildanalys.
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2010 (Engelska)Ingår i: Aging Cell, ISSN 1474-9718, E-ISSN 1474-9726, Vol. 9, nr 5, s. 685-697Artikel i tidskrift (Refereegranskat) Published
Fritextbeskrivning
Abstract [en]

The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging- and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21–31 years) and nine old men (72–96 years), and from six young (24–32 years) and nine old women (65–96 years), using a novel image analysis algorithm applied to confocal images. Muscle fibres were classified according to myosin heavy chain (MyHC) isoform expression. Our image analysis algorithm was effective in determining the spatial organization of myonuclei and the distribution of individual MNDs along the single fibre segments. Significant linear relations were observed between MND size and fibre size, irrespective age, gender and MyHC isoform expression. The spatial organization of individual myonuclei, calculated as the distribution of nearest neighbour distances in 3D, and MND size were affected in old age, but changes were dependent on MyHC isoform expression. In type I muscle fibres, average NN-values were lower and showed an increased variability in old age, reflecting an aggregation of myonuclei in old age. Average MND size did not change in old age, but there was an increased MND size variability. In type IIa fibres, average NN-values and MND sizes were lower in old age, reflecting the smaller size of these muscle fibres in old age. It is suggested that these changes have a significant impact on protein synthesis and degradation during the aging process.

Ort, förlag, år, upplaga, sidor
2010. Vol. 9, nr 5, s. 685-697
Nyckelord [en]
aging, human skeletal muscle, myonuclear domain, 3D imaging
Nationell ämneskategori
Fysiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-139870DOI: 10.1111/j.1474-9726.2010.00594.xISI: 000281897400003PubMedID: 20633000OAI: oai:DiVA.org:uu-139870DiVA, id: diva2:382335
Tillgänglig från: 2010-12-30 Skapad: 2010-12-30 Senast uppdaterad: 2018-12-02Bibliografiskt granskad
Ingår i avhandling
1. Myonuclear Organization and Regulation of Muscle Contraction in Single Muscle Fibres: Effects of Ageing, Gender, Species, Endocrine Factors and Muscle Size
Öppna denna publikation i ny flik eller fönster >>Myonuclear Organization and Regulation of Muscle Contraction in Single Muscle Fibres: Effects of Ageing, Gender, Species, Endocrine Factors and Muscle Size
2012 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of cytoplasm i.e., the myonuclear domain (MND). A novel image analysis algorithm applied to confocal images, analyzing MND size and myonuclear spatial distribution in 3-dimensions in single skeletal muscle fibres has been used in this project. The goal was to explore the modulation of myonuclei count and MND size in response to muscle adaptation processes. The effects of ageing, gender, hormones, muscle hypertrophy and body size were investigated on MND size.

A strong linear relationship was found between MND size and body size in the muscle fibres from mammals representing a 100,000-fold difference in body size. Independent of species, MND size was highly dependent on MyHC isoform type and mitochondrial contents of skeletal muscle fibres. In hypertrophic mice, a significant effect of MND size on specific force and myosin content was observed. This effect was muscle fibre type-specific and shows that the bigger MNDs in fast-twitch EDL muscle fibres are optimally tuned for force production while smaller MNDs in slow-twitch soleus muscle fibres have a much more dynamic range of hypertrophy without functional compromise. This indicates a critical volume individual myonuclei can support efficiently for a proportional gain in muscle fibre force and size. In human muscle fibres, spatial organization of myonuclei was affected by both ageing and MyHC isoform expression. In fibres expressing type I MyHC isoform, an increased MND size variability and myonuclear aggregates were observed in old age although average MND size was unchanged. In contrast, in type IIa fibres, the average MND size was smaller reflecting smaller size of muscle fibres. Those changes may influence the transcriptional activity per myonucleus and/or local cooperatively of myonuclei in a gender and muscle fibre-type specific manner. Finally, hormone replacement therapy was shown to negate menopause-related functional impairment in skeletal muscle fibres. The positive effect on force was due to quantitative effect in fibres expressing fast myosin isoform while the effect was both quantitative and qualitative in fibres expressing slow myosin isoform. The effect on MND size was fibre type dependent and was achieved by significantly reducing domain size in slow- but not the fast-twitch muscle fibres.

Together, our data suggest that modulation of myonuclei count and MND size is a mechanism contributing to remodelling of skeletal muscle in muscle adaptation process. These findings should be considered when developing therapeutic approaches towards restoring muscle mass and strength in muscle wasting conditions.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2012. s. 62
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 737
Nyckelord
single muscle cells, muscle nuclei, specific force, species, hypertrophy, mammals, ageing, gender
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
Fysiologi
Identifikatorer
urn:nbn:se:uu:diva-167723 (URN)978-91-554-8264-0 (ISBN)
Disputation
2012-03-15, Hedstrandsalen, Ingång 70, bv,AS Akademiska sjukhuset, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2012-02-28 Skapad: 2012-02-01 Senast uppdaterad: 2018-01-12Bibliografiskt granskad

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Qaisar, RizwanBengtsson, EwertLarsson, Lars

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