Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level

Takahashi, Hironobu; Nakamura, Asuka; Shimizu, Tatsuya

doi:10.1016/j.bbrc.2021.09.037

Cited by 18 publications

(22 citation statements)

References 31 publications

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“…Current literature suggests that the DNA double strand break and increase in sumoylation can drive and balance the senescence process [67,68]. This might explain the increase in sµG induced cellular senescence which has been reported in many mammalian cells [69][70][71]. On the other hand, there were much fewer enriched pathways in resting T cells in 3D cell culture under sμG conditions compared to 1g.…”

Section: Resting T Cellsmentioning

confidence: 95%

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

ElGindi

Sapudom

Laws

et al. 2022

Cell. Mol. Life Sci.

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Human space travel and exploration are of interest to both the industrial and scientific community.However, there are many adverse effects of spaceflight on human physiology. In particular, there is a lack of understanding to the extent by which microgravity affects the immune system. T cells, key players of the adaptive immune system and long term immunity, are present not only in blood circulation, but also reside within tissue. As of yet, studies investigating the effects of microgravity on T cells are limited to peripheral blood or traditional 2D cell culture that recapitulates circulating blood. To better mimic interstitial tissue, 3D cell culture has been well established for physiologically and pathologically relevant models. In this work, we utilize 2D and 3D cell culture to gain an understanding of how simulated microgravity affects both circulating and tissue resident T cells. T cells were studied in both resting and activated stages. We found that 3D cell culture attenuates the effects of simulated microgravity on the T cells transcriptome and nuclear irregularities compared to 2D cell culture. Interestingly, simulated microgravity appears to have less effect on activated T cells compared to those in the resting stage. Overall, our work provides novel insights into the effects of simulated microgravity on circulating and tissue resident T cells which could provide benefits for the health of space travelers.

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Section: Resting T Cellsmentioning

confidence: 95%

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

ElGindi

Sapudom

Laws

et al. 2022

Cell. Mol. Life Sci.

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“…Others have suggested that simulated microgravity in vitro induces senescence via mitochondrial dysfunction and oxidative stress in mesenchymal stem cells[43], skeletal muscle myoblasts[44], and neural crest-derived rat pheochromocytoma cells[45]. However, it should be noted that our model of disuse only occurred over three weeks.…”

Section: Discussionmentioning

confidence: 93%

Hindlimb Unloading Induces Bone Microarchitectural and Transcriptomic Changes in Murine Long Bones in an Age-Dependent Manner

Meas,

Daire,

Friedman

et al. 2023

Preprint

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Age and disuse-related bone loss both result in decreases in bone mineral density, cortical thickness, and trabecular thickness and connectivity. Disuse induces physiological changes in bone like those seen with aging. Bone microarchitecture and biomechanical properties were compared between 6- and 22-month-old C57BL/6J male control mice and 6-month-old mice that were hindlimb unloaded (HLU) for 3 weeks. Epiphyseal trabecular bone was the compartment most affected by HLU and demonstrated an intermediate bone phenotype between age-matched controls and aged controls. RNA extracted from whole-bone marrow-flushed tibiae was sequenced and analyzed. Differential gene expression analysis additionally included 4-month-old male mice unloaded for 3 weeks compared to age-matched controls. Gene ontology analysis demonstrated that there were age-dependent differences in differentially expressed genes. Genes related to downregulation of cellular processes were most affected in 4-month-old mice after disuse whereas those related to mitochondrial function were most affected in 6-month-old mice. Cell-cycle transition was downregulated with aging. A publicly available dataset (GSE169292) from 3-month female C57BL/6N mice unloaded for 7 days was included in ingenuity pathway analysis with the other datasets. IPA was used to identify the leading canonical pathways and upstream regulators in each HLU age group. IPA identified Senescence Pathway as the second leading canonical pathway enriched in mice exposed to HLU. HLU induced activation of the senescence pathway in 3-month and 4-month-old mice but inhibited it in 6-month-old mice. In conclusion, we demonstrate that hindlimb unloading and aging initiate similar changes in bone microarchitecture and gene expression. However, aging is responsible for more significant transcriptome and tissue-level changes compared to hindlimb unloading.

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“…Microgravity may affect ER morphology, remodeling, and function by impairing the oocyte cytoskeleton [40]. Finally, since the presence of numerous, large MV complexes represents an ultrastructural marker of aging (both in vitro and in vivo aging), we cannot exclude that simulated microgravity may act as "accelerating" the aging of the oocytes in the RPM machine, mimicking what happens on human systems, organs and tissues subjected to a microgravity environment in the space and on the ground [41,42].…”

Section: Discussionmentioning

confidence: 99%

Effects of Simulated Microgravity In Vitro on Human Metaphase II Oocytes: An Electron Microscopy-Based Study

Miglietta

Cristiano

Espinola

et al. 2023

Cells

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The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria–vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocytes.

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Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level

Cited by 18 publications

References 31 publications

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

3D microenvironment attenuates simulated microgravity-mediated changes in T cell transcriptome

Hindlimb Unloading Induces Bone Microarchitectural and Transcriptomic Changes in Murine Long Bones in an Age-Dependent Manner

Effects of Simulated Microgravity In Vitro on Human Metaphase II Oocytes: An Electron Microscopy-Based Study

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