Abstract：
: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.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Andersson DC,Betzenhauser MJ,Reiken S,Meli AC,Umanskaya A,Xie W,Shiomi T,Zalk R,Lacampagne A,Marks ARdoi
10.1016/j.cmet.2011.05.014subject
Has Abstractpub_date
2011-08-03 00:00:00pages
196-207issue
2eissn
1550-4131issn
1932-7420pii
S1550-4131(11)00255-5journal_volume
14pub_type
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