title: Long live FOXO: unraveling the role of FOXO proteins in aging and longevity.
abstract: Aging constitutes the key risk factor for age-related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which "protective genes" are carried by long-lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin-like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Martins
authors.affiliation: The Buck Institute for Research on Aging, Novato, CA, 94945, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Lithgow
authors.affiliation: Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.|Centre for Biomedical Research (CBMR), University of Algarve, Campus de Gambelas, 8005-139, Faro, Portugal.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Link
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D008136:Longevity / Q000235:genetics*; D023421:Models, Animal; D015398:Signal Transduction
chemical_list: D051858:Forkhead Transcription Factors
keywords: FOXO transcription factors; aging; animal models; insulin and IGF-1 signaling pathway; longevity