Aging Effects of Caenorhabditis elegans Ryanodine Receptor Variants Corresponding to Human Myopathic Mutations
نویسندگان
چکیده
Delaying the decline in skeletal muscle function will be critical to better maintenance of an active lifestyle in old age. The skeletal muscle ryanodine receptor, the major intracellular membrane channel through which calcium ions pass to elicit muscle contraction, is central to calcium ion balance and is hypothesized to be a significant factor for age-related decline in muscle function. The nematode Caenorhabditis elegans is a key model system for the study of human aging, and strains were generated with modified C. elegans ryanodine receptors corresponding to human myopathic variants linked with malignant hyperthermia and related conditions. The altered response of these strains to pharmacological agents reflected results of human diagnostic tests for individuals with these pathogenic variants. Involvement of nerve cells in the C. elegans responses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications in C. elegans also conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging.
منابع مشابه
Caenorhabditis elegans as a model organism for RYR1 variants and muscle ageing
Background Malignant hyperthermia (MH), central core disease (CCD), exertional heat stroke (EHS) and late-onset axial myopathy have been attributed to mutations in ryanodine receptor type 1 (RYR1). The RyR1 protein is over 5000 amino acid residues long, making manipulation of the mammalian gene difficult. The ryanodine receptor in Caenorhabditis elegans is UNC-68, which has 40% amino acid ident...
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