Can FOXOs modulate longevity?
['Forkhead box O (FOXO) transcription factors have a conserved function in regulating metazoan lifespan.', 'In contrast to FoxO1, FoxO3a and FoxO6 were specifically diminished in the CNS of HFD animals possibly contributing to the reduced lifespan observed in these animals.', 'Interestingly, many target proteins of AMPK are so-called longevity factors, e.g., SIRT1, p53, and FoxOs, which not only can increase the stress resistance and extend the lifespan of many organisms but also inhibit the inflammatory responses. ', 'Components of anti-ageing and autophagy include SirTs and FoxOs.', 'Since Sirts and FoxOs are reliable markers of longevity, the results appear to suggest that Longevinex induces longevity after prolonged feeding via induction of autophagy, while it converts death signals into survival signals and provides cardioprotection within a relatively shorter period of time.', 'Forkhead box O (FOXO) transcription factors are involved in various cellular processes, including cell proliferation, stress resistance, metabolism, and longevity', 'In this respect, members of the mammalian forkhead transcription factors of the O class (FoxOs) that include FoxO1, FoxO3, FoxO4 and FoxO6 are increasingly being recognized as exciting prospects for multiple disorders. These transcription factors govern development, proliferation, survival and longevity during multiple cellular environments that can involve oxidative stress. ', 'Here we discuss the fascinating but complex role of FoxOs during cellular injury and oxidative stress, progenitor cell development, fertility, angiogenesis, cardiovascular function, cellular metabolism and diabetes, cell longevity, immune surveillance and cancer.', 'Many longevity genes, e.g. FoxOs and SIRT1, are inhibitors of NF-kappaB signaling. ', 'Interestingly, several longevity genes such as SIRT1, SIRT6, and FoxOs can clearly suppress NF-kappaB signaling and in this way delay the aging process and extend lifespan.', 'Yet, FoxOs also can significantly affect normal cell survival and longevity, requiring new treatments for neoplastic growth to modulate novel pathways that integrate cell proliferation, metabolism, inflammation and survival.', 'These observations link FoxO function in mammalian systems with the evolutionarily conserved role of FoxO in promotion of stress resistance and longevity in lower phylogenetic systems. Furthermore, these findings have implications for aging in higher organisms and in malignant stem cell biology, and suggest that FoxOs may play an important role in the maintenance and integrity of stem cell compartments in a broad spectrum of tissues.', 'Forkhead box O (FoxO) transcription factors are important downstream targets of the PI3K/Akt signaling pathway and crucial regulators of cell fate. This function of FoxOs relies on their ability to control diverse cellular functions, including proliferation, differentiation, apoptosis, DNA repair, defense against oxidative stress and ageing.', 'This brief review focuses on the molecular mechanisms, cellular effects and resulting organismal phenotypes generated by differentially regulated FoxO proteins and discusses our current understanding of the role of FoxOs in disease and ageing processes.', 'In this review, we focus on the several interactions of aging-associated signaling cascades regulated either by Sirtuins and FoxOs or NF-kappaB signaling pathways. We provide evidence that signaling via the longevity factors of FoxOs and SIRT1 can inhibit NF-kappaB signaling and simultaneously protect against inflamm-aging process.', 'In diverse species transcription factors belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have been found to be crucial in downstream suppression of the life-shortening effects of insulin/insulin-like growth factor-I receptor signalling pathways that, when upregulated, accelerate ageing by suppression of FOXO. ', 'In humans, FOXO3a, as well as FOXO1 and -4, and their downstream effectors, could hold the key to counteracting ageing and common diseases.', 'FOXO transcription factors have important roles in metabolism, cellular proliferation, stress tolerance, and aging. ']
['FOXOs are reliable markers of longevity.']
['yes']