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Skeletal muscle size and strength decline in older age. The vastus lateralis, a large thigh muscle, undergoes extensive neuromuscular remodelling in healthy ageing, as characterized by a loss of motor neurons, enlargement of surviving motor units and instability of neuromuscular junction transmission. The loss of motor axons and changes to motor unit potential transmission precede a clinically-relevant loss of muscle mass and function.
The Gene Ontology (GO) Consortium (GOC, http://www.geneontology.org) is a community-based bioinformatics resource that classifies gene product function through the use of structured, controlled vocabularies. Over the past year, the GOC has implemented several processes to increase the quantity, quality and specificity of GO annotations. First, the number of manual, literature-based annotations has grown at an increasing rate. Second, as a result of a new 'phylogenetic annotation' process, manually reviewed, homology-based annotations are becoming available for a broad range of species. Third, the quality of GO annotations has been improved through a streamlined process for, and automated quality checks of, GO annotations deposited by different annotation groups. Fourth, the consistency and correctness of the ontology itself has increased by using automated reasoning tools. Finally, the GO has been expanded not only to cover new areas of biology through focused interaction with experts, but also to capture greater specificity in all areas of the ontology using tools for adding new combinatorial terms. The GOC works closely with other ontology developers to support integrated use of terminologies. The GOC supports its user community through the use of e-mail lists, social media and web-based resources.
Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
The age-related loss of muscle mass is related to the loss of innervating motor neurons and denervation of muscle fibres. Not all denervated muscle fibres are degraded; some may be reinnervated by an adjacent surviving neuron, which expands the innervating motor unit proportional to the numbers of fibres rescued. Enlarged motor units have larger motor unit potentials when measured using electrophysiological techniques. We recorded much larger motor unit potentials in relatively healthy older men compared to young men, but the older men with the smallest muscles (sarcopenia) had smaller motor unit potentials than healthy older men. These findings suggest that healthy older men reinnervate large numbers of muscle fibres to compensate for declining motor neuron numbers, but a failure to do so contributes to muscle loss in sarcopenic men.
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