Aging Effects ofCaenorhabditis elegansRyanodine Receptor Variants Corresponding to Human Myopathic Mutations.
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 nematodeCaenorhabditis elegansis a key model system for the study of human aging, and strains were generated with modifiedC. elegansryanodine 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 theC. elegansresponses may relate to rare medical symptoms concerning the central nervous system that have been associated with ryanodine receptor variants. These single amino acid modifications inC. elegansalso conferred a reduction in lifespan and an accelerated decline in muscle integrity with age, supporting the significance of ryanodine receptor function for human aging.
Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, LS9 7TF, United Kingdom bsknb@leeds.ac.uk M.Shaw@leeds.ac.uk i.a.hope@leeds.ac.uk.|School of Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom.
Baines K
Baines K
Nicoll
School of Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom.
Célia
0000-0003-1190-4323
C
Ferreira
Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, LS9 7TF, United Kingdom.
Philip M
0000-0002-8127-1739
PM
Hopkins
Leeds Institute of Biomedical and Clinical Sciences, St James's University Hospital, LS9 7TF, United Kingdom bsknb@leeds.ac.uk M.Shaw@leeds.ac.uk i.a.hope@leeds.ac.uk.
Marie-Anne
MA
Shaw
School of Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom bsknb@leeds.ac.uk M.Shaw@leeds.ac.uk i.a.hope@leeds.ac.uk.
Ian A
0000-0002-8990-3163
IA
Hope
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D009135:Muscular Diseases / Q000235:genetics*; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D019837:Ryanodine Receptor Calcium Release Channel; C438601:Unc-68 protein, C elegans
Caenorhabditis elegans; aging; malignant hyperthermia; muscle; ryanodine receptor