scholarly journals Serine and glycine are essential for human muscle progenitor cell population expansion

2019 ◽  
Author(s):  
Brandon J. Gheller ◽  
Jamie E. Blum ◽  
Erica L. Bender ◽  
Mary E. Gheller ◽  
Esther W. Lim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Amino Acid ◽  
Muscle Regeneration ◽  
Adult Stem Cells ◽  
De Novo ◽  
Population Expansion ◽  
Skeletal Muscle Regeneration ◽  
Dependent Manner ◽  
Older Individuals ◽  
Age Related

SummarySkeletal muscle regeneration is reliant on a population of muscle specific adult stem cells (muscle progenitor cells; MPCs). During regeneration, the MPC population undergoes a transient and rapid period of population expansion, which is necessary to repair damaged myofibers and restore muscle homeostasis. Much research has focused on the age-related accumulation of negative regulators of regeneration, while the age-related decline of nutrient and metabolic determinants of the regenerative process needs examination. We hypothesized that older individuals, a population that is at risk for protein malnutrition, have diminished availability of amino acids that are necessary for MPC function. Here, we identified that levels of the non-essential amino acid serine are reduced in the skeletal muscle of healthy, older individuals. Furthermore, using stable-isotope tracing studies, we demonstrate that primary, human MPCs (hMPCs) exhibit a limited capacity for de novo biosynthesis of serine and the closely related amino acid glycine. We identified that serine and glycine are essential for hMPC proliferation and, therefore, population expansion. Serine and glycine were necessary to support synthesis of the intracellular antioxidant glutathione, and restriction of serine and glycine was sensed in an EIF2α-dependent manner resulting in cell cycle arrest in G0/G1. In conclusion, we elucidate that, despite an absolute requirement of serine/glycine for hMPC proliferation, availability of serine in the skeletal muscle microenvironment is limited to the hMPCs of healthy older adults and is a likely underlying mechanism for impaired skeletal muscle regeneration with advancing age. Graphical Abstract

scholarly journals Comparative transcriptomic analysis of dermal wound healing reveals de novo skeletal muscle regeneration in Acomys cahirinus

PLoS ONE ◽  
2019 ◽  
Vol 14 (5) ◽  
pp. e0216228 ◽  
Author(s):  
Jason O. Brant ◽  
J. Lucas Boatwright ◽  
Ruth Davenport ◽  
Aaron Gabriel W. Sandoval ◽  
Malcolm Maden ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Wound Healing ◽  
Muscle Regeneration ◽  
De Novo ◽  
Transcriptomic Analysis ◽  
Skeletal Muscle Regeneration ◽  
Acomys Cahirinus ◽  
Dermal Wound Healing ◽  
Dermal Wound ◽  
Comparative Transcriptomic Analysis

Skeletal Muscle Regeneration, Repair and Remodelling in Aging: The Importance of Muscle Stem Cells and Vascularization

Gerontology ◽  
2016 ◽  
Vol 63 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Sophie Joanisse ◽  
Joshua P. Nederveen ◽  
Tim Snijders ◽  
Bryon R. McKay ◽  
Gianni Parise
Keyword(s):  
Older Adults ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Mass ◽  
Muscle Regeneration ◽  
Skeletal Muscle Mass ◽  
Financial Burden ◽  
Skeletal Muscle Regeneration ◽  
Age Related ◽  
Aging Muscle

Sarcopenia is the age-related loss of skeletal muscle mass and strength. Ultimately, sarcopenia results in the loss of independence, which imposes a large financial burden on healthcare systems worldwide. A critical facet of sarcopenia is the diminished ability for aged muscle to regenerate, repair and remodel. Over the years, research has focused on elucidating underlying mechanisms of sarcopenia and the impaired ability of muscle to respond to stimuli with aging. Muscle-specific stem cells, termed satellite cells (SC), play an important role in maintaining muscle health throughout the lifespan. It is well established that SC are essential in skeletal muscle regeneration, and it has been hypothesized that a reduction and/or dysregulation of the SC pool, may contribute to accelerated loss of skeletal muscle mass that is observed with advancing age. The preservation of skeletal muscle tissue and its ability to respond to stimuli may be impacted by reduced SC content and impaired function observed with aging. Aging is also associated with a reduction in capillarization of skeletal muscle. We have recently demonstrated that the distance between type II fibre-associated SC and capillaries is greater in older compared to younger adults. The greater distance between SC and capillaries in older adults may contribute to the dysregulation in SC activation ultimately impairing muscle's ability to remodel and, in extreme circumstances, regenerate. This viewpoint will highlight the importance of optimal SC activation in addition to skeletal muscle capillarization to maximize the regenerative potential of skeletal muscle in older adults.

Cellular and Molecular Regulation of Muscle Regeneration

2004 ◽  
Vol 84 (1) ◽  
pp. 209-238 ◽  
Author(s):  
SOPHIE B. P. CHARGÉ ◽  
MICHAEL A. RUDNICKI
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Satellite Cell ◽  
Muscle Regeneration ◽  
Adult Stem Cells ◽  
Cell Activation ◽  
De Novo ◽  
Molecular Regulation ◽  
Muscle Repair ◽  
Adult Skeletal Muscle

Chargé, Sophie B. P., and Michael A. Rudnicki. Cellular and Molecular Regulation of Muscle Regeneration. Physiol Rev 84: 209–238, 2004; 10.1152/physrev.00019.2003.—Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the remarkable ability to initiate a rapid and extensive repair process preventing the loss of muscle mass. Skeletal muscle repair is a highly synchronized process involving the activation of various cellular responses. The initial phase of muscle repair is characterized by necrosis of the damaged tissue and activation of an inflammatory response. This phase is rapidly followed by activation of myogenic cells to proliferate, differentiate, and fuse leading to new myofiber formation and reconstitution of a functional contractile apparatus. Activation of adult muscle satellite cells is a key element in this process. Muscle satellite cell activation resembles embryonic myogenesis in several ways including the de novo induction of the myogenic regulatory factors. Signaling factors released during the regenerating process have been identified, but their functions remain to be fully defined. In addition, recent evidence supports the possible contribution of adult stem cells in the muscle regeneration process. In particular, bone marrow-derived and muscle-derived stem cells contribute to new myofiber formation and to the satellite cell pool after injury.

Age-Related Dysregulation of Hypoxia Signaling Limits Skeletal Muscle Regeneration in Aging

2020 ◽  
Vol 231 (4) ◽  
pp. S305
Author(s):  
Yori Endo ◽  
Kodi Baldino ◽  
Bin Li ◽  
Yuteng Zhang ◽  
Dharaniya Sakthivel ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Regeneration ◽  
Skeletal Muscle Regeneration ◽  
Age Related ◽  
Hypoxia Signaling

scholarly journals Transferrin receptor (Tfr1) ablation in satellite cells impacts skeletal muscle regeneration through the activation of ferroptosis

2020 ◽  
Author(s):  
Hongrong Ding ◽  
Shujie Chen ◽  
Xiaohan Pan ◽  
Xiaoshuang Dai ◽  
Guihua Pan ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Iron Accumulation ◽  
Skeletal Muscle Regeneration ◽  
Acid Biosynthesis ◽  
Labile Iron

AbstractSatellite cells (SCs) are critical to the postnatal development and skeletal muscle regeneration. Inactivation of SCs is linked with the skeletal muscle loss. Leveraging on the RNAseq screening, transferrin receptor (Tfr1) is identified to be associated with muscle/SC ageing and the declined regeneration potential. Muscle-specific deletion of Tfr1 results in the growth retardation, metabolic disorder and lethality, shedding light on the importance of Tfr1 in skeletal muscle physiology. Here, our investigation reported that conditional SC-ablation of Tfr1 leads to the SCs inactivation and skeletal muscle regeneration defects, followed by the labile iron accumulation, de novo lipogenesis via fibroadipogenic progenitors (FAPs) and Gpx4/Nrf2-mediated ROS-scavenger defects. These abnormal phenomena, such as Hmox1-mediated myoglobin degradation, Tfr1-Slc39a14 functional switch and the activation of unsaturated fatty acid biosynthesis pathway are orchestrated with the occurrence of ferroptosis in skeletal muscle. Ferroptosis may further prevent SC proliferation and skeletal muscle regeneration. Ferrostatin-1, a ferroptosis inhibitor could not rescue Tfr1-ablation induced ferroptosis. However, intramuscular administration of lentivirus expressing Tfr1 could partially reduce labile iron accumulation, decrease de novo lipogenesis and promote skeletal muscle regeneration. Most importantly, Tfr1/Slc39a14 functional switch, labile iron accumulation and fatty acid biosynthesis are recapitulated in aged skeletal muscle of rodents, indicating that ferroptosis occurs in the skeletal muscles of aged rodents. The present study also bridges the gap between pathogenesis of iron and functional defects in the skeletal muscle, providing mechanistic information to develop anti-aging strategies.One Sentence SummaryConditional ablation of Tfr1 in satellite cells (SCs) results in the SC inactivation, skeletal muscle regeneration defects, labile iron accumulation, and unsaturated fatty acid biosynthesis, leading to the activation of ferroptosis, which is recapitulated in skeletal muscles of aged rodents to be a new cell death form identified in skeletal muscle and sheds light on the development of novel anti-ageing strategies.

scholarly journals Adult Stem Cells and Skeletal Muscle Regeneration

2015 ◽  
Vol 15 (4) ◽  
pp. 348-363 ◽  
Author(s):  
Domiziana Costamagna ◽  
Emanuele Berardi ◽  
Gabriele Ceccarelli ◽  
Maurilio Sampaolesi
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Muscle Regeneration ◽  
Adult Stem Cells ◽  
Skeletal Muscle Regeneration
Sign in / Sign up

Export Citation Format

Share Document