Myonuclear content regulates cell size with similar scaling properties in mice and humans

Hansson, Kenth-Arne; Eftestøl, Einar; Bruusgaard, Jo C.; Juvkam, Inga Solgård; Cramer, Alyssa; Malthe‐Sørenssen, Anders; Millay, Douglas P.; Gundersen, Kristian

doi:10.1038/s41467-020-20057-8

Cited by 57 publications

(64 citation statements)

References 80 publications

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“…4) ). As we have suggested previously such flexibility might be related to either the number of nuclei limiting the maximum fiber size (Hansson, Eftestøl et al 2020), or the presence of some form of cooperativity between nuclei increasing their ability to produce volume (Cramer, Prasad et al 2020).…”

Section: Discussionmentioning

confidence: 84%

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

Ochi

et al. 2021

Preprint

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One of the ideas stemming from the discovery of a cellular memory in muscle cells has been that an early exercise period could induce a long-term muscle memory, boosting the effects of exercise later in life. In general muscles are more plastic in younger animals, so we devised a 5-week climbing exercise scheme with food reward administered to juvenile rats (post-natal week 4-9). The juvenile exercise increased fiber cross-sectional area (fCSA), and boosted nuclear accretion. Subsequently the animals were subjected to 10 weeks of detraining (week 9-19, standard caging). During this period fCSA became similar in the animals that had been climbing compared to Naive controls, but the elevated number of myonuclei induced by the climbing were maintained. When the Naive rats were subjected to two weeks of adult exercise (week 19-21) there was little effect on fCSA, while the previously trained rats displayed an increase of 19%. Similarly, when the rats were subjected to unilateral surgical overload in lieu of the adult climbing exercise, the increase in fCSA was 20% (juvenile climbing group) and 11% (Naive rats) compared to the contralateral leg. This demonstrated that juvenile exercise can establish a muscle memory. The juvenile climbing exercise with food reward led to leaner animals with lower body weight. These differences were to some extent maintained throughout the adult detraining period in spite of all animals being fed ad libitum, indicating a form of body weight memory.

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Section: Discussionmentioning

confidence: 84%

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

Ochi

et al. 2021

Preprint

Self Cite

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“…We propose that the impact of nuclear morphology and nuclear mechanotransduction in skeletal muscle homeostasis and adaptation is an area worthy of further investigation. To date, most of the work in skeletal muscle has focused on nuclear abundance as an important determinant of myofiber size and adaptation ( McCarthy et al, 2011 ; Murach et al, 2017 ; Psilander et al, 2019 ; Cramer et al, 2020 ; Hansson et al, 2020 ), with almost no focus on the nucleus as being a central player in the mechanotransduction response to mechanical load. The importance of nuclear mechanotransduction and the LINC complex in nuclear migration during myogenesis is well established ( Zhang et al, 2010 ; Gimpel et al, 2017 ; Stroud et al, 2017 ), yet whether this importance persists for tissue maintenance is unclear.…”

Section: Important Considerations and Future Directionsmentioning

confidence: 99%

LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function

Ingen

Kirby

2021

Front. Cell Dev. Biol.

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Skeletal muscle demonstrates a high degree of adaptability in response to changes in mechanical input. The phenotypic transformation in response to mechanical cues includes changes in muscle mass and force generating capabilities, yet the molecular pathways that govern skeletal muscle adaptation are still incompletely understood. While there is strong evidence that mechanotransduction pathways that stimulate protein synthesis play a key role in regulation of muscle mass, there are likely additional mechano-sensitive mechanisms important for controlling functional muscle adaptation. There is emerging evidence that the cell nucleus can directly respond to mechanical signals (i.e., nuclear mechanotransduction), providing a potential additional level of cellular regulation for controlling skeletal muscle mass. The importance of nuclear mechanotransduction in cellular function is evident by the various genetic diseases that arise from mutations in proteins crucial to the transmission of force between the cytoskeleton and the nucleus. Intriguingly, these diseases preferentially affect cardiac and skeletal muscle, suggesting that nuclear mechanotransduction is critically important for striated muscle homeostasis. Here we discuss our current understanding for how the nucleus acts as a mechanosensor, describe the main cytoskeletal and nuclear proteins involved in the process, and propose how similar mechanoresponsive mechanisms could occur in the unique cellular environment of a myofiber. In addition, we examine how nuclear mechanotransduction fits into our current framework for how mechanical stimuli regulates skeletal muscle mass.

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“…However, interestingly, the reserve capacity is reduced in myofibers harboring 75% of myonuclei; thus, the myofiber size was similarly reduced to that of the myofibers with half the nuclei [ 68 ]. It has also been demonstrated that the number of myonuclei defines the size of myofibers in both humans and mice [ 69 ]. These studies also indicate the critical roles of myonuclear number and MuSCs, because MuSC is also responsible for the increase in myonuclear number during the developmental stage [ 70 ].…”

Section: Critical Roles Of Myonuclei Number For Size Of Myofibersmentioning

confidence: 99%

Exercise/Resistance Training and Muscle Stem Cells

Fukada

Nakamura

2021

Endocrinol Metab

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Skeletal muscle has attracted attention as endocrine organ, because exercise-dependent cytokines called myokines/exerkines are released from skeletal muscle and are involved in systemic functions. While, local mechanical loading to skeletal muscle by exercise or resistance training alters myofiber type and size and myonuclear number. Skeletal muscle-resident stem cells, known as muscle satellite cells (MuSCs), are responsible for the increased number of myonuclei. Under steady conditions, MuSCs are maintained in a mitotically quiescent state but exit from that state and start to proliferate in response to high physical activity. Alterations in MuSC behavior occur when myofibers are damaged, but the lethal damage to myofibers does not seem to evoke mechanical loading-dependent MuSC activation and proliferation. Given that MuSCs proliferate without damage, it is unclear how the different behaviors of MuSCs are controlled by different physical activities. Recent studies demonstrated that myonuclear number reflects the size of myofibers; hence, it is crucial to know the properties of MuSCs and the mechanism of myonuclear accretion by MuSCs. In addition, the elucidation of mechanical load-dependent changes in muscle resident cells, including MuSCs, will be necessary for the discovery of new myokines/exerkines and understating skeletal muscle diseases.

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Myonuclear content regulates cell size with similar scaling properties in mice and humans

Cited by 57 publications

References 80 publications

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

A juvenile climbing exercise establishes a muscle memory boosting the effects of exercise in adult rats

LINCing Nuclear Mechanobiology With Skeletal Muscle Mass and Function

Exercise/Resistance Training and Muscle Stem Cells

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