Human muscle stem cells are refractory to aging

Novak, James S.; Mázala, Davi A. G.; Nearing, Marie; Hindupur, Ravi; Uapinyoying, Prech; Habib, Nayab F.; Dickson, Tessa; Ioffe, Olga B.; Harris, Brent T.; Fidelia-Lambert, Marie; Rossi, Christopher T.; Hill, Daniel; Wagner, Kathryn R.; Hoffman, Eric P.; Partridge, Terence A.

doi:10.1111/acel.13411

Cited by 22 publications

(11 citation statements)

References 48 publications

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“…Indeed, despite their limited availability and local migratory potential, it is becoming increasingly clear that well-defined and highly myogenic MuSCs could be a feasible, safe, and efficacious cell source for autologous cell replacement therapies to treat muscle-wasting disorders. 13 , 20 , 34 , 35 , 36 , 37 Obtaining large numbers of highly regenerative ex vivo expanded primary MuSCs for autologous therapies is still a challenge, but significant progress has been made in recent years. 13 , 34 , 38 , 39 The number of cells needed for the functional reconstitution of human muscles has yet to be determined and may depend on many factors related to both the fitness of the transplanted cells and the environment of the recipient muscle.…”

Section: Discussionmentioning

confidence: 99%

mRNA-mediated delivery of gene editing tools to human primary muscle stem cells

Stadelmann

Francescantonio

Marg

et al. 2022

Molecular Therapy - Nucleic Acids

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Section: Discussionmentioning

confidence: 99%

mRNA-mediated delivery of gene editing tools to human primary muscle stem cells

Stadelmann

Francescantonio

Marg

et al. 2022

Molecular Therapy - Nucleic Acids

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“…SGs also play an important role in mitigating the negative consequences of sarcopenia and improving muscle function ( 11 ). The physiological role of SGs is to provide nuclei to existing myofibers, thereby enhancing or maintaining transcriptional capacity ( 87 ). The physiological role of SGs in mediating adaptations to exercise remains a contentious issue.…”

Section: The Mechanisms Underlying Bfrt In Treating Sarcopeniamentioning

confidence: 99%

Blood Flow Restriction Training for the Intervention of Sarcopenia: Current Stage and Future Perspective

et al. 2022

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Sarcopenia is a geriatric syndrome that is characterized by a progressive and generalized skeletal muscle disorder and can be associated with many comorbidities, including obesity, diabetes, and fracture. Its definitions, given by the AWGS and EWGSOP, are widely used. Sarcopenia is measured by muscle strength, muscle quantity or mass and physical performance. Currently, the importance and urgency of sarcopenia have grown. The application of blood flow restriction (BFR) training has received increased attention in managing sarcopenia. BFR is accomplished using a pneumatic cuff on the proximal aspect of the exercising limb. Two main methods of exercise, aerobic exercise and resistance exercise, have been applied with BFR in treating sarcopenia. Both methods can increase muscle mass and muscle strength to a certain extent. Intricate mechanisms are involved during BFRT. Currently, the presented mechanisms mainly include responses in the blood vessels and related hormones, such as growth factors, tissue hypoxia-related factors and recruitment of muscle fiber as well as muscle satellite cells. These mechanisms contribute to the positive balance of skeletal muscle synthesis, which in turn mitigates sarcopenia. As a more suited and more effective way of treating sarcopenia and its comorbidities, BFRT can serve as an alternative to traditional exercise for people who have marked physical limitations or even show superior outcomes under low loads. However, the possibility of causing stress or muscle damage must be considered. Cuff size, pressure, training load and other variables can affect the outcome of sarcopenia, which must also be considered. Thoroughly studying these factors can help to better determine an ideal BFRT scheme and better manage sarcopenia and its associated comorbidities. As a well-tolerated and novel form of exercise, BFRT offers more potential in treating sarcopenia and involves deeper insights into the function and regulation of skeletal muscle.

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“…In several animal models, the regenerative capacity of skeletal muscle declines with age, largely due to the senescence of MuSCs [30][31][32][33] . However, the extent of MuSC functional decline in human ageing remains a controversial topic 34,35 . To better understand their age-related transcriptional changes, we performed unsupervised clustering of the 15,606 high-quality MuSCs across ages from the scRNA-seq data subset and identified 4 subpopulations (Fig.…”

Section: Mechanistic Insights Into Human Musc Ageingmentioning

confidence: 99%

Human skeletal muscle ageing atlas

Kedlian

Wang

Liu

et al. 2022

Preprint

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Skeletal muscle ageing increases the incidence of age-associated frailty and sarcopenia in the elderly worldwide, leading to increased morbidity and mortality. However, our understanding of the cellular and molecular mechanisms of muscle ageing is still far from complete. Here, we generate a single-cell and single-nucleus transcriptomic atlas of skeletal muscle ageing from 15 donors across the adult human lifespan, accompanied by myofiber typing using imaging. Our atlas reveals ageing mechanisms acting across different compartments of the muscle, including muscle stem cells (MuSCs), myofibers and the muscle microenvironment. Firstly, we uncover two mechanisms driving MuSC ageing, namely a decrease in ribosome biogenesis and an increase in inflammation. Secondly, we identify a set of nuclei populations explaining the preferential degeneration of the fast-twitch myofibers and suggest two mechanisms acting to compensate for their loss. Importantly, we identify a neuromuscular junction accessory population, which helps myofiber to compensate for aged-related denervation. Thirdly, we reveal multiple microenvironment cell types contributing to the inflammatory milieu of ageing muscle by producing cytokines and chemokines to attract immune cells. Finally, we provide a comparable mouse muscle ageing atlas and further investigate conserved and specific ageing hallmarks across species. In summary, we present a comprehensive human skeletal muscle ageing resource by combining different data modalities, which significantly expands our understanding of muscle biology and ageing.

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Human muscle stem cells are refractory to aging

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 22 publications

References 48 publications

mRNA-mediated delivery of gene editing tools to human primary muscle stem cells

mRNA-mediated delivery of gene editing tools to human primary muscle stem cells

Blood Flow Restriction Training for the Intervention of Sarcopenia: Current Stage and Future Perspective

Human skeletal muscle ageing atlas

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