Biol Chem. 2012 Nov 16. pii: /j/bchm.just-accepted/hsz-2012-0247/hsz-2012-0247.xml. doi: 10.1515/hsz-2012-0247. [Epub ahead of print]
Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy.
Abstract
Abstract Muscle loss during aging and disuse is a highly prevalent and disabling condition, but the knowledge about cellular pathways mediating muscle atrophy is still limited. Given the postmitotic nature of skeletal myocytes, the maintenance of cellular homeostasis relies on the efficiency of cellular quality control mechanisms. In this scenario, alterations in mitochondrial function are considered a major factor underlying sarcopenia and disuse muscle wasting. Damaged mitochondria not only are less bioenergetically efficient, but also generate increased amounts of reactive oxygen species, interfere with cellular quality control mechanisms, and display greater propensity to trigger apoptosis. Thus, mitochondria stand at the crossroad of signaling pathways that regulate skeletal myocyte function and viability. Studies on these pathways have sometimes provided unexpected and counterintuitive results, suggesting that they are organized into a complex, heterarchical network that is currently insufficiently understood. Untangling the complexity of such network will likely provide clinicians with novel and highly effective therapeutics to counter muscle loss associated with aging and disuse. In this review, we summarize the current knowledge on the mechanisms whereby mitochondrial dysfunction intervenes in the pathogenesis of sarcopenia and disuse atrophy, and highlight the prospect of targeting specific processes to treat these conditions.
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