Single Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging

Murgia, Marta; Toniolo, Luana; Nagaraj, Nagarjuna; Ciciliot, Stefano; Vindigni, Vincenzo; Schiaffino, Stefano; Reggiani, Carlo; Mann, Matthias

doi:10.1016/j.celrep.2017.05.054

Cited by 243 publications

(319 citation statements)

References 66 publications

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“…So far, most myofiber analyses have been limited to MFI binning, which is driven by the categories made by eye assessment. This results in myofiber categories defining myofibers as negative or positive to a specific MyHC isoform (6,7,9,12,(23)(24)(25)(26). Hence, classic myofiber typing does not capture the full spectrum of myofiber variation, and most studies define myofiber type based on fast-twitch (expressing MyHC-2b) or slowtwitch (expressing MyHC-1/2a) characteristics (9,27).…”

Section: Discussionmentioning

confidence: 99%

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High‐throughput data‐driven analysis of myofiber composition reveals muscle‐specific disease and age‐associated patterns

Raz

Vijver

et al. 2018

FASEB j.

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Contractile properties of myofibers are dictated by the abundance of myosin heavy chain (MyHC) isoforms. MyHC composition designates muscle function, and its alterations could unravel differential muscle involvement in muscular dystrophies and aging. Current analyses are limited to visual assessments in which myofibers expressing multiple MyHC isoforms are prone to misclassification. As a result, complex patterns and subtle alterations are unidentified. We developed a high‐throughput, data‐driven myofiber analysis to quantitatively describe the variations in myofibers across the muscle. We investigated alterations in myofiber composition between genotypes, 2 muscles, and 2 age groups. We show that this analysis facilitates the discovery of complex myofiber compositions and its dependency on age, muscle type, and genetic conditions.—Raz, V., Raz, Y., van de Vijver, D., Bindellini, D., van Putten, M., van den Akker, E. B. High‐throughput data‐driven analysis of myofiber composition reveals muscle‐specific disease and age‐associated patterns. FASEB J. 33, 4046–4053 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

“…Classically, myofiber characteristics are determined based on a visual assessment of MyHC expression and are often categorized on the basis of the expression of a single and most dominant isoform only (7,(9)(10)(11). In addition, visual assessments are subjective because the number of myofibers that can be scored is limited.…”

mentioning

confidence: 99%

High‐throughput data‐driven analysis of myofiber composition reveals muscle‐specific disease and age‐associated patterns

Raz

Vijver

et al. 2018

FASEB j.

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“…Very sensitive workflows have begun to apply LC-MS/MS to small samples comprising hundreds of human cells [60] and even to large single cells, such as oocytes [65,66] and muscle fibers [67,68]. These applications developed and applied very sensitive methods to quantitate between 450 and 800 proteins in single human oocytes, and ~2100 proteins in single muscle fibers.…”

Section: Ms-based Methodsmentioning

confidence: 99%

Single cell protein analysis for systems biology

Levy

Slavov

2018

Essays in Biochemistry

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The cellular abundance of proteins can vary even between isogenic single cells. This variability between single-cell protein levels can have regulatory roles, such as controlling cell fate during apoptosis induction or the proliferation/quiescence decision. Here, we review examples connecting protein levels and their dynamics in single cells to cellular functions. Such findings were made possible by the introduction of antibodies, and subsequently fluorescent proteins, for tracking protein levels in single cells. However, in heterogeneous cell populations, such as tumors or differentiating stem cells, cellular decisions are controlled by hundreds, even thousands of proteins acting in concert. Characterizing such complex systems demands measurements of thousands of proteins across thousands of single cells. This demand has inspired the development of new methods for single-cell protein analysis, and we discuss their trade-offs, with an emphasis on their specificity and coverage. We finish by highlighting the potential of emerging mass-spec methods to enable systems-level measurement of single-cell proteomes with unprecedented coverage and specificity. Combining such methods with methods for quantitating the transcriptomes and metabolomes of single cells will provide essential data for advancing quantitative systems biology.

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“…In recent years, human proteomic analysis has focused on major contractile proteins, such as myosin heavy chains, and other key proteins involved in metabolism and protein homeostasis in the different muscle fiber types . Proteomic analysis of muscle fiber from aged individuals (65–75 years) showed that aged muscle fibers have lower protein levels for all five mitochondria protein complexes compared to young individuals (22–27 years), with fast type 2A fibers tend have larger decrease than slow type 1 fibers.…”

Section: Proteomics Studiesmentioning

confidence: 99%

Sarcopenia: Tilting the Balance of Protein Homeostasis

2019

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Sarcopenia, defined as age‐associated decline of muscle mass and function, is a risk factor for mortality and disability, and comorbid with several chronic diseases such as type II diabetes and cardiovascular diseases. Clinical trials showed that nutritional supplements had positive effects on muscle mass, but not on muscle function and strength, demonstrating our limited understanding of the molecular events involved in the ageing muscle. Protein homeostasis, the equilibrium between protein synthesis and degradation, is proposed as the major mechanism underlying the development of sarcopenia. As the key central regulator of protein homeostasis, the mammalian target of rapamycin (mTOR) is proposed to be essential for muscle hypertrophy. Paradoxically, sustained activation of mTOR complex 1 (mTORC1) is associated with a loss of sensitivity to extracellular signaling in the elderly. It is not understood why sustained mTORC1 activity, which should induce muscle hypertrophy, instead results in muscle atrophy. Here, recent findings on the implications of disrupting protein homeostasis on muscle physiology and sarcopenia development in the context of mTOR/protein kinase B (AKT) signaling are reviewed. Understanding the role of these molecular mechanisms during the ageing process will contribute towards the development of targeted therapies that will improve protein metabolism and reduce sarcopenia.

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Single Muscle Fiber Proteomics Reveals Fiber-Type-Specific Features of Human Muscle Aging

Cited by 243 publications

References 66 publications

High‐throughput data‐driven analysis of myofiber composition reveals muscle‐specific disease and age‐associated patterns

High‐throughput data‐driven analysis of myofiber composition reveals muscle‐specific disease and age‐associated patterns

Single cell protein analysis for systems biology

Sarcopenia: Tilting the Balance of Protein Homeostasis

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