The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
Ryanodine Receptor Oxidation Causes Intracellular Calcium Leak and Muscle Weakness in Aging
Open accessAbstract
Age-related loss of muscle mass and force (sarcopenia) contributes to disability and increased mortality. Ryanodine receptor 1 (RyR1) is the skeletal muscle sarcoplasmic reticulum calcium release channel required for muscle contraction. RyR1 from aged (24 months) rodents was oxidized, cysteine-nitrosylated, and depleted of the channel-stabilizing subunit calstabin1, compared to RyR1 from younger (3-6 months) adults. This RyR1 channel complex remodeling resulted in "leaky" channels with increased open probability, leading to intracellular calcium leak in skeletal muscle. Similarly, 6-month-old mice harboring leaky RyR1-S2844D mutant channels exhibited skeletal muscle defects comparable to 24-month-old wild-type mice. Treating aged mice with S107 stabilized binding of calstabin1 to RyR1, reduced intracellular calcium leak, decreased reactive oxygen species (ROS), and enhanced tetanic Ca(2+) release, muscle-specific force, and exercise capacity. Taken together, these data indicate that leaky RyR1 contributes to age-related loss of muscle function.
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“An increase in Ca2+ concentration induces mPTP opening, which further exacerbates the imbalance of intracellular Ca2+ homeostasis, possibly caused by leaky ryanodine receptors in aged skeletal muscle (49).”
From From mitochondria to sarcopenia: role of 17β-estradiol and testosterone (2023) · cites this paper as [49]
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Cites
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Structure of a mammalian ryanodine receptor
Zalk, R., Clarke, O. B., Georges, A. D., Grassucci, R. A., Reiken, S. R., Mancia, F., Hendrickson, W. A., Frank, J., & Marks, A. R. (2014) · Nature · doi:10.1038/nature13950 · Cited by 439
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Metadata
- Authors
- Andersson, D. C., Betzenhauser, M. J., Reiken, S., Meli, A. C., Umanskaya, A., Xie, W., Shiomi, T., Zalk, R., Lacampagne, A., & Marks, A. R.
- Affiliations
- Columbia University Irving Medical Center (US)
- Inserm (FR)
- Corresponding author
- Marks, Andrew R.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 14
- Issue
- 2
- Pages
- 196-207
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3690519
- OpenAlex
- W2078833625
- Cited by
- 424
- References
- 73
- Citations by year
- 2026: 24 · 2025: 31 · 2024: 28 · 2023: 33 · 2022: 36 · 2021: 29 · 2020: 36 · 2019: 22 · 2018: 26 · 2017: 25 · 2016: 33 · 2015: 24 · 2014: 25 · 2013: 34 · 2012: 16
- FWCI
- 9.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vetenskapsrådet
- National Heart, Lung, and Blood Institute (R01HL056180, R01HL061503)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR060037)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- RyR1, sarcopenia, aging, skeletal muscle, reactive oxygen species, muscle weakness, calcium release channel, exercise capacity, muscle force
- MeSH terms
- Aging, Animals, Calcium, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Motor Activity, Muscle Contraction, Oxidation-Reduction, Thiazepines, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Muscle Weakness, Ryanodine Receptor Calcium Release Channel, Tacrolimus Binding Proteins, Mice, Sarcopenia
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