scholarly journals Enhanced exercise and regenerative capacity in a mouse model that violates size constraints of oxidative muscle fibres

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Saleh Omairi ◽  
Antonios Matsakas ◽  
Hans Degens ◽  
Oliver Kretz ◽  
Kenth-Arne Hansson ◽  
...  

A central tenet of skeletal muscle biology is the existence of an inverse relationship between the oxidative fibre capacity and its size. However, robustness of this relationship is unknown. We show that superimposition of Estrogen-related receptor gamma (Errγ) on the myostatin (Mtn) mouse null background (Mtn-/-/ErrγTg/+) results in hypertrophic muscle with a high oxidative capacity thus violating the inverse relationship between fibre size and oxidative capacity. We also examined the canonical view that oxidative muscle phenotype positively correlate with Satellite cell number, the resident stem cells of skeletal muscle. Surprisingly, hypertrophic fibres from Mtn-/-/ErrγTg/+ mouse showed satellite cell deficit which unexpectedly did not affect muscle regeneration. These observations 1) challenge the concept of a constraint between fibre size and oxidative capacity and 2) indicate the important role of the microcirculation in the regenerative capacity of a muscle even when satellite cell numbers are reduced.

1988 ◽  
Vol 20 (4) ◽  
pp. 291-295 ◽  
Author(s):  
STEPHANIE VALBERG ◽  
BIRGITTA ESSÉN GUSTAVSSON ◽  
HELENA SKOGLUND WALLBERG

2011 ◽  
Vol 366 (1575) ◽  
pp. 2297-2306 ◽  
Author(s):  
Jennifer L. Shadrach ◽  
Amy J. Wagers

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.


Author(s):  
Silvia Campanario ◽  
Ignacio Ramírez-Pardo ◽  
Xiaotong Hong ◽  
Joan Isern ◽  
Pura Muñoz-Cánoves

The skeletal muscle tissue in the adult is relatively stable under normal conditions but retains a striking ability to regenerate by its resident stem cells (satellite cells). Satellite cells exist in a quiescent (G0) state; however, in response to an injury, they reenter the cell cycle and start proliferating to provide sufficient progeny to form new myofibers or undergo self-renewal and returning to quiescence. Maintenance of satellite cell quiescence and entry of satellite cells into the activation state requires autophagy, a fundamental degradative and recycling process that preserves cellular proteostasis. With aging, satellite cell regenerative capacity declines, correlating with loss of autophagy. Enhancing autophagy in aged satellite cells restores their regenerative functions, underscoring this proteostatic activity’s relevance for tissue regeneration. Here we describe two strategies for assessing autophagic activity in satellite cells from GFP-LC3 reporter mice, which allows direct autophagosome labeling, or from non-transgenic (wild-type) mice, where autophagosomes can be immunostained. Treatment of GFP-LC3 or WT satellite cells with compounds that interfere with autophagosome-lysosome fusion enables measurement of autophagic activity by flow cytometry and immunofluorescence. Thus, the methods presented permit a relatively rapid assessment of autophagy in stem cells from skeletal muscle in homeostasis and in different pathological scenarios such as regeneration, aging or disease.


2009 ◽  
Vol 40 (3) ◽  
pp. 455-465 ◽  
Author(s):  
Abigail L. Mackey ◽  
Michael Kjaer ◽  
Nadia Charifi ◽  
Jan Henriksson ◽  
Jens Bojsen-Moller ◽  
...  

Rangifer ◽  
1986 ◽  
Vol 6 (2) ◽  
pp. 2 ◽  
Author(s):  
K.-H. Kiessling ◽  
A. Kiessling ◽  
K. Nilssen ◽  
I.-L. Andersson

<p>Enzyme activities and fibre properties in four muscles from Svalbard reindeer, collected during the summer, have been compared with corresponding muscles during the winter. In two muscles, gluteobiceps and semimembranosus, oxidative capacity is higher in winter than in summer; in the other two muscles, semitendinosus and longissimus dorsi, there is no difference with time of the year. The capacity to oxidize fatty acids is low in winter compared with summer, especially in semitendinosus and longissimus. These changes are similar in both sexes. Histochemical studies of the three main fibre types, I (BetaR), HA (&deg;cR) and IIB (aW), from the four muscles show that in male reindeers the muscle fibres are narrower at the end of the winter season than during the summer. The decrease of muscle tissue amounts to about one third of the total volume (33%), of which I accounts for 5%, IIA for 2% and IIB for 26%. The results indicate that the Svalbard reindeer use lean tissue in general, and IIB fibres in particular, in order to survive the hostile arctic winter period at Svalbard.</p><p>Histokemiska och enzymatiska skillnader i skelettmuskel fr&aring;n Svalbardren mellan sommar och vinter.</p><p>Abstract in Swedish / Sammandrag: Enzymaktiviteter och fiberegenskaper i fyra av Svalbardrenens muskler, insamlade under sommaren, har j&aring;mforts med motsvarande muskler insamlade under vintern. I tv&aring; muskler, gluteobiceps och semimembranosus, &aring;r oxidativa kapaciteten hogre under vintern an under sommaren; i de andra tv&aring; musklerna, semitendinosus och longissimus dorsi, foreligger ingen skillnad i detta avseende. Kapaciteten att oxidera fettsyror &aring;r l&aring;g under vintern j&aring;mfort med sommaren, speciellt i semitendinosus och longissimus. Inga konsskillnader foreligger i dessa avseenden. Histokemiska studier av de tre huvudtyperna av muskelfibrer, fiR (I), ocR (IIA) och (IIB), fr&aring;n de fyra musklerna visar att hos handjuren &aring;r fibrerna tunnare vid slutet av vinters&aring;songen j&aring;mfort med sommaren. Denna minskning i muskelv&aring;vnad uppg&aring;r till en tredjedel av totala volymen (33%). Harav svarar ftR for 5%, ^R tor 2% och for 26%. Resultaten antyder att Svalbardrenen anv&aring;nder muskelv&aring;vnad, speciellt QcW fibrer, for att overleva undri den h&aring;rda arktiska vinterperioden p&aring; Svalbard.</p>


2006 ◽  
Vol 91 (8) ◽  
pp. 3024-3033 ◽  
Author(s):  
Indrani Sinha-Hikim ◽  
Marcia Cornford ◽  
Hilda Gaytan ◽  
Martin L. Lee ◽  
Shalender Bhasin

Abstract Objective: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. Participants: Healthy men, 60–75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. Methods: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. Results: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P &lt; 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P &lt; 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P &lt; 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P &lt; 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. Conclusions: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.


2016 ◽  
Vol 55 (3) ◽  
pp. 384-392 ◽  
Author(s):  
Matthew C. Kinney ◽  
Sudarshan Dayanidhi ◽  
Peter B. Dykstra ◽  
John J. McCarthy ◽  
Charlotte A. Peterson ◽  
...  

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