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Age-related diseases are typically preceded by loss of muscle strength, but the mechanisms of age-related muscle weakness and their contribution to systemic ageing were unknown. Using Drosophila as a model, Demontis and Perrimon now demonstrate that impaired function of ageing muscles is associated with the progressive accumulation of protein aggregates. Specifically, they found that the transcription factor FOXO and its target, 4E-BP, were required for the removal of damaged proteins from muscle tissue (i.e. for maintenance of normal muscle proteostasis), and FOXO-deficient flies had abnormal muscle proteostasis. By contrast, muscle-specific overexpression of FOXO preserved muscle function, extended life span, and reduced feeding and insulin secretion, which in turn slowed the accumulation of protein aggregates in other tissues with age. These findings indicate that FOXO–4E-BP signalling in muscle regulates systemic tissue ageing, opening up new avenues for therapies that prevent age-related muscle degeneration and extend life span.
Demontis F., Perrimon N. ( 2010). FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143, 813– 825 [PubMed]