bims-mitrat 2024-09-01 papers

bims-mitrat

Biomed News

on Mitochondrial Transplantation and Transfer

Issue of 2024‒09‒01
twelve papers selected by
Gökhan Burçin Kubat, Gulhane Health Sciences Institute

Mitochondrial heterogeneity and crosstalk in aging: Time for a paradigm shift?
Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.
Stroke Studies in Large Animals: Prospects of Mitochondrial Transplantation and Enhancing Efficiency using Hydrogels and Nanoparticle-assisted Delivery.
Mitochondrial membrane lipids in the regulation of bioenergetic flux.
Mitochondria: fundamental characteristics, challenges, and impact on aging.
Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.
Mitochondrial free radicals contribute to cigarette smoke condensate-induced impairment of oxidative phosphorylation in the skeletal muscle in situ.
Targeting organ-specific mitochondrial dysfunction to improve biological aging.
Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen.
Extracellular vesicle therapy in neurological disorders.
Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis.
Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg.

Aging Cell. 2024 Aug 26. e14296

Mitochondrial heterogeneity and crosstalk in aging: Time for a paradigm shift?

Antentor O Hinton, Zer Vue, Estevão Scudese, Kit Neikirk, Annet Kirabo, Monty Montano.

  The hallmarks of aging have been influential in guiding the biology of aging research, with more recent and growing recognition of the interdependence of these hallmarks on age-related health outcomes. However, a current challenge is personalizing aging trajectories to promote healthy aging, given the diversity of genotypes and lived experience. We suggest that incorporating heterogeneity-including intrinsic (e.g., genetic and structural) and extrinsic (e.g., environmental and exposome) factors and their interdependence of hallmarks-may move the dial. This editorial perspective will focus on one hallmark, namely mitochondrial dysfunction, to exemplify how consideration of heterogeneity and interdependence or crosstalk may reveal new perspectives and opportunities for personalizing aging research. To this end, we highlight heterogeneity within mitochondria as a model.

Keywords:  aging; mitochondria; organelle contacts; protein targeting; structure

DOI:  https://doi.org/10.1111/acel.14296
Exp Physiol. 2024 Aug 24.

Skeletal muscle myosin heavy chain fragmentation as a potential marker of protein degradation in response to resistance training and disuse atrophy.

Daniel L Plotkin, Madison L Mattingly, Derick A Anglin, J Max Michel, Joshua S Godwin, Mason C McIntosh, Nicholas J Kontos, João G A Bergamasco, Maíra C Scarpelli, Vitor Angleri, Lemuel W Taylor, Darryn S Willoughby, C Brooks Mobley, Andreas N Kavazis, Carlos Ugrinowitsch, Cleiton A Libardi, Michael D Roberts.

  We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post-RE (∼200%, P = 0.018) and returned to pre-exercise levels by 6 h post-RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post-RE (8.6 ± 6.3-fold vs. 2.1 ± 0.7-fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post-RE (+65% and +36%, P < 0.001); however, the last RE bout response was attenuated compared to the first bout (P = 0.045). Although cycling exercise did not alter MyHCTotal fragmentation, ∼8% VL atrophy with 2 weeks of leg immobilization increased MyHCTotal fragmentation (∼108%, P < 0.001). Mechanistic C2C12 myotube experiments indicated that MyHCTotal fragmentation is likely due to calpain proteases. In summary, RE and disuse atrophy increase MyHC protein fragmentation. Research into how ageing and disease-associated muscle atrophy affect these outcomes is needed. HIGHLIGHTS: What is the central question of this study? How different exercise stressors and disuse affect skeletal muscle myosin heavy chain fragmentation. What is the main finding and its importance? This investigation is the first to demonstrate that resistance exercise and disuse atrophy lead to skeletal muscle myosin heavy chain protein fragmentation in humans. Mechanistic in vitro experiments provide additional evidence that MyHC fragmentation occurs through calpain proteases.

Keywords:  immunoblotting; myosin heavy chain; proteolysis; resistance exercise; skeletal muscle

DOI:  https://doi.org/10.1113/EP092093
Ageing Res Rev. 2024 Aug 25. pii: S1568-1637(24)00287-3. [Epub ahead of print] 102469

Stroke Studies in Large Animals: Prospects of Mitochondrial Transplantation and Enhancing Efficiency using Hydrogels and Nanoparticle-assisted Delivery.

Oner Ulger, Ismail Eş, Christopher M Proctor, Oktay Algin.

  One of the most frequent reasons of mortality and disability today is acute ischemic stroke, which occurs by an abrupt disruption of cerebral circulation. The intricate damage mechanism involves several factors, such as inflammatory response, disturbance of ion balance, loss of energy production, excessive reactive oxygen species and glutamate release, and finally, neuronal death. Stroke research is now carried out using several experimental models and potential therapeutics. Furthermore, studies are being conducted to address the shortcomings of clinical care. A great deal of research is being done on novel pharmacological drugs, mitochondria targeting compounds, and different approaches including brain cooling and new technologies. Still, there are many unanswered questions about disease modeling and treatment strategies. Before these new approaches may be used in therapeutic settings, they must first be tested on large animals, as most of them have been done on rodents. However, there are several limitations to large animal stroke models used for research. In this review, the damage mechanisms in acute ischemic stroke and experimental acute ischemic stroke models are addressed. The current treatment approaches and promising experimental methods such as mitochondrial transplantation, hydrogel-based interventions, and strategies like mitochondria encapsulation and chemical modification, are also examined in this work.

Keywords:  Acute ischemic stroke; endovascular stroke models; hydrogels; large animal stroke models; mitochondria modification; mitochondrial transplantation

DOI:  https://doi.org/10.1016/j.arr.2024.102469
Cell Metab. 2024 Aug 13. pii: S1550-4131(24)00326-7. [Epub ahead of print]

Mitochondrial membrane lipids in the regulation of bioenergetic flux.

Stephen Thomas Decker, Katsuhiko Funai.

  Oxidative phosphorylation (OXPHOS) occurs through and across the inner mitochondrial membrane (IMM). Mitochondrial membranes contain a distinct lipid composition, aided by lipid biosynthetic machinery localized in the IMM and class-specific lipid transporters that limit lipid traffic in and out of mitochondria. This unique lipid composition appears to be essential for functions of mitochondria, particularly OXPHOS, by its effects on direct lipid-to-protein interactions, membrane properties, and cristae ultrastructure. This review highlights the biological significance of mitochondrial lipids, with a particular spotlight on the role of lipids in mitochondrial bioenergetics. We describe pathways for the biosynthesis of mitochondrial lipids and provide evidence for their roles in physiology, their implications in human disease, and the mechanisms by which they regulate mitochondrial bioenergetics.

Keywords:  bioenergetics; mitochondria; phospholipids

DOI:  https://doi.org/10.1016/j.cmet.2024.07.024
Biogerontology. 2024 Aug 28.

Mitochondria: fundamental characteristics, challenges, and impact on aging.

Runyu Liang, Luwen Zhu, Yongyin Huang, Jia Chen, Qiang Tang.

  As one of the most vital organelles within biological cells, mitochondria hold an irreplaceable status and play crucial roles in various diseases. Research and therapies targeting mitochondria have achieved significant progress in numerous conditions. Throughout an organism's lifespan, mitochondrial dynamics persist continuously, and due to their inherent characteristics and various external factors, mitochondria are highly susceptible to damage. This susceptibility is particularly evident during aging, where the decline in biological function is closely intertwined with mitochondrial dysfunction. Despite being an ancient and enigmatic organelle, much remains unknown about mitochondria. Here, we will explore the past and present knowledge of mitochondria, providing a comprehensive review of their intrinsic properties and interactions with nuclear DNA, as well as the challenges and impacts they face during the aging process.

Keywords:  Aging; Endosymbiosis; Mitochondria; Mitochondria DNA; Nuclear DNA

DOI:  https://doi.org/10.1007/s10522-024-10132-8
Biomedicines. 2024 Aug 01. pii: 1705. [Epub ahead of print]12(8):

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

Santiago J Miyara, Koichiro Shinozaki, Kei Hayashida, Muhammad Shoaib, Rishabh C Choudhary, Stefanos Zafeiropoulos, Sara Guevara, Junhwan Kim, Ernesto P Molmenti, Bruce T Volpe, Lance B Becker.

  The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Keywords:  astrocytes; cardiac arrest; hypothermia; ischemia-reperfusion injury; neurons; neuroprotection

DOI:  https://doi.org/10.3390/biomedicines12081705
Free Radic Biol Med. 2024 Aug 21. pii: S0891-5849(24)00617-8. [Epub ahead of print]

Mitochondrial free radicals contribute to cigarette smoke condensate-induced impairment of oxidative phosphorylation in the skeletal muscle in situ.

Sean T Bannon, Stephen T Decker, Muhammet Enes Erol, Rong Fan, Yu-Ting Huang, Soonkyu Chung, Gwenael Layec.

  Oxidative stress plays a critical role in cellular dysfunction associated with cigarette smoke exposure and aging. Some chemicals from tobacco smoke have the potential to amplify mitochondrial ROS (mROS) production, which, in turn, may impair mitochondrial respiratory function. Accordingly, the present study tested the hypothesis that a mitochondria-targeted antioxidant (MitoTEMPO, MT) would attenuate the inhibitory effects of cigarette smoke on skeletal muscle respiratory capacity of middle-aged mice. Specifically, mitochondrial oxidative phosphorylation was assessed using high-resolution respirometry in permeabilized fibers from the fast-twitch gastrocnemius muscle of middle-aged C57Bl/6 mice. Before the assessment of respiration, tissues were incubated for 1hr with a control buffer (CON), cigarette smoke condensate (2% dilution, SMOKE), or MitoTEMPO (10μM) combined with cigarette smoke condensate (MT+SMOKE). Cigarette smoke condensate (CSC) decreased maximal-ADP stimulated respiration (CON: 60±15 pmolO2.s-1.mg-1 and SMOKE: 33±8 pmolO2.s-1.mg-1; p=0.0001), and this effect was attenuated by MT (MT+SMOKE: 41±7 pmolO2.s-1.mg-1; p=0.02 with SMOKE). Complex-I specific respiration was inhibited by CSC, with no significant effect of MT (p=0.35). Unlike CON, the addition of glutamate (ΔGlutamate) had an additive effect on respiration in fibers exposed to CSC (CON: 0.9±1.1 pmolO2.s-1.mg-1 and SMOKE: 5.4±3.7 pmolO2.s-1.mg-1; p=0.008) and MT (MT+SMOKE: 8.2±3.8 pmolO2.s-1.mg-1; p≤0.01). Complex-II specific respiration was inhibited by CSC but was partially restored by MT (p=0.04 with SMOKE). Maximal uncoupled respiration induced by FCCP was inhibited by CSC, with no significant effect of MT. These findings underscore that mROS contributes to cigarette smoke condensate-induced inhibition of mitochondrial respiration in fast-twitch gastrocnemius muscle fibers of middle-aged mice thus providing a potential target for therapeutic treatment of smoke-related diseases. In addition, this study revealed that CSC largely impaired muscle respiratory capacity by decreasing metabolic flux through mitochondrial pyruvate transporter (MPC) and/or the enzymes upstream of α-ketoglutarate in the Krebs cycle.

Keywords:  High-Resolution Respirometry; Mito-TEMPO; Skeletal muscle; aging; cigarette smoke; redox stress

DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.08.024
Pharmacol Ther. 2024 Aug 22. pii: S0163-7258(24)00130-X. [Epub ahead of print]262 108710

Targeting organ-specific mitochondrial dysfunction to improve biological aging.

Corina T Madreiter-Sokolowski, Ursula Hiden, Jelena Krstic, Katrin Panzitt, Martin Wagner, Christian Enzinger, Michael Khalil, Mahmoud Abdellatif, Ernst Malle, Tobias Madl, Elena Osto, Markus Schosserer, Christoph J Binder, Andrea Olschewski.

  In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function. The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues. In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.

Keywords:  Anti-aging strategies; Mitochondrial dysfunction; Organ-specific aging; ROS homeostasis; Therapeutic interventions

DOI:  https://doi.org/10.1016/j.pharmthera.2024.108710
Biomolecules. 2024 Aug 02. pii: 939. [Epub ahead of print]14(8):

Skeletal Muscle-Derived Stem Cell Transplantation Accelerates the Recovery of Peripheral Nerve Gap Injury under 50% and 100% Allogeneic Compatibility with the Swine Leucocyte Antigen.

Tetsuro Tamaki, Toshiharu Natsume, Akira Katoh, Atsuko Shigenari, Takashi Shiina, Nobuyuki Nakajima, Kosuke Saito, Tsuyoshi Fukuzawa, Masayoshi Otake, Satoko Enya, Akihisa Kangawa, Takeshi Imai, Miyu Tamaki, Yoshiyasu Uchiyama.

  Pig skeletal muscle-derived stem cells (SK-MSCs) were transplanted onto the common peroneal nerve with a collagen tube as a preclinical large animal experiment designed to address long nerve gaps. In terms of therapeutic usefulness, a human family case was simulated by adjusting the major histocompatibility complex to 50% and 100% correspondences. Swine leukocyte antigen (SLA) class I haplotypes were analyzed and clarified, as well as cell transplantation. Skeletal muscle-derived CD34+/45- (Sk-34) cells were injected into bridged tubes in two groups (50% and 100%) and with non-cell groups. Therapeutic effects were evaluated using sedentary/general behavior-based functional recovery score, muscle atrophy ratio, and immunohistochemistry. The results indicated that a two-Sk-34-cell-transplantation group showed clearly and significantly favorable functional recovery compared to a non-cell bridging-only group. Supporting functional recovery, the morphological reconstitution of the axons, endoneurium, and perineurium was predominantly evident in the transplanted groups. Thus, Sk-34 cell transplantation is effective for the regeneration of peripheral nerve gap injury. Additionally, 50% and 100% SLA correspondences were therapeutically similar and not problematic, and no adverse reaction was found in the 50% group. Therefore, the immunological response to Sk-MSCs is considered relatively low. The possibility of the Sk-MSC transplantation therapy may extend to the family members beyond the autologous transplantation.

Keywords:  allogeneic cellular therapy; cloning; micro-mini pig; preclinical large animal experiment; swine leukocyte antigen haplotypes

DOI:  https://doi.org/10.3390/biom14080939
J Biomed Sci. 2024 Aug 25. 31(1): 85

Extracellular vesicle therapy in neurological disorders.

Napasiri Putthanbut, Jea Young Lee, Cesario V Borlongan.

  Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations. EV therapy shows promise in stimulating tissue repair and serving as a drug delivery vehicle, offering advantages over cell therapy, such as ease of engineering and minimal risk of tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, and underdeveloped large-scale production protocols. This review highlights the recent advances and significance of EVs heterogeneity, emphasizing the need for a better understanding of their roles in disease pathologies to develop tailored EV therapies for clinical applications in neurological disorders.

Keywords:  EVs; Extracellular vesicle therapy; Neurological disorders; Regenerative therapy

DOI:  https://doi.org/10.1186/s12929-024-01075-w
Nat Commun. 2024 Aug 26. 15(1): 7337

Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis.

Niranjana Natarajan, Jonathan Florentin, Ebin Johny, Hanxi Xiao, Scott Patrick O'Neil, Liqun Lei, Jixing Shen, Lee Ohayon, Aaron R Johnson, Krithika Rao, Xiaoyun Li, Yanwu Zhao, Yingze Zhang, Sina Tavakoli, Sruti Shiva, Jishnu Das, Partha Dutta.

There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe-/- mice lacking Vcam1 in macrophages. Downregulation of macrophage-specific VCAM-1 in vivo leads to decreased expression of LYZ1 and FCOR, involved in STING signalling. Finally, VCAM-1 expression in human carotid plaque macrophages correlates with necrotic core area, mitochondrial volume, and oxidative damage to DNA. Collectively, our study highlights the importance of macrophage VCAM-1 in inflammation and atherogenesis pathology and proposes a self-acerbating pathway involving increased mtDNA synthesis.

DOI: https://doi.org/10.1038/s41467-024-51780-1
J Cachexia Sarcopenia Muscle. 2024 Aug 26.

Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg.

Edward J Hardy, Joseph J Bass, Thomas B Inns, Mathew Piasecki, Jessica Piasecki, Craig Sale, Robert H Morris, Jonathan N Lund, Ken Smith, Daniel J Wilkinson, Philip J Atherton, Bethan E Phillips.

  BACKGROUND: Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work.METHODS: To address this significant knowledge gap, 10 young men (22 ±  years, 24.1 ± 2.3 kg/m2) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI.
RESULTS: With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSAMRI vs. MTU/S and CSAU/S: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOLMRI vs. MTU/S and CSAU/S: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSAMRI vs. MTU/S: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOLMRI: 136 ± 6 vs. 133 ± 5, P = 0.08; CSAU/S: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75).
CONCLUSIONS: Both MTU/S and CSAU/S provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MTU/S and CSAU/S can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body.

Keywords:  Disuse; Imaging; MRI; Muscle; Ultrasound

DOI:  https://doi.org/10.1002/jcsm.13583