FOXO transcription factors in the regulatory networks of longevity

FOXO (Forkhead box O) transcription factors constitute an evolutionally conserved subgroup within the large Forkhead family of transcription regulators. FOXO factors are important regulators of the cell cycle, apoptosis, DNA repair, metabolism, oxidative stress resistance and longevity. Genetic studies of Caenorhabditis elegans demonstrated that FOXO factors are major targets of the insulin-like signalling implicated during the regulation of glucose metabolism and lifespan extension. Recently, emerging evidence has also shed light on signalling pathways under oxidative stress that regulate FOXO activity by various post-translational modifications, including phosphorylation, acetylation and ubiquitination. Thus, FOXO factors react to external stimuli by altering their modifications, modulating target gene expression that may be involved in longevity.