FOXO3

• OMIM: 602 681
• UniProt: O43524

The forkhead box protein O3 ( FOXO3, older names include FOXO3A, FKHRL1 or AF6q21 ) is a transcription factor in animals and fungi, which is encoded in humans by the FOXO3 gene. The FOXO3 gene is frequently referred to in popular or non-scientific publications as aging gene, Greisen- gene or Methuselah gene.

Location, structure and function

The gene product of FOXO3 belongs to the family of forkhead box proteins. It is a transcription factor that attaches itself in the nucleus to specific sites on DNA and so affects the transcription of genes. To FOXO family includes humans still FOXO1, FOXO4 and FOXO6.

The FOXO3 gene is located on chromosome 6 in humans locus q21. A pseudogene is p11 gene locus on chromosome 17. FOXO3 consists of at least three exons and two introns. It is at least 90 kb. The gene consists of 673 amino acids.

Acute food deprivation in mice causes increased expression of sirtuin -1 and FOXO3. Wherein the resistance of the cell is increased to the oxidative stress. Switching off the FOXO3 gene ( gene knockout ) causes the enzyme sirtuin -1 is not upregulated in food deprivation. The stimulation of the sirtuin - 1 transcription is mediated by two FOXO3 by p53 binding sites in the sirtuin -1 promoter.

FOXO3 and aging

Stress- activated protein kinases such as p38, JNK and the expression of FOXO3 can stimulate. This in turn leads to a reduced cell growth and reduced cell division, inter alia by inhibition of Akt / PKB. The cell goes into a state of quiescence. FOXO3 also increases the expression of antioxidant enzymes manganese superoxide dismutase ( MnSOD ) and iron superoxide dismutase ( FeSOD ), and catalase. However FOXO3 can also set the apoptosis (programmed cell death) in motion.

For quite a stir caused in 2009 a study by a research group led by the researchers from Kiel Friederike flat beard, Almut Nebel and Stefan Schreiber, were compared with the DNA samples from 388 German centenarians with 731 younger people. Striking was the fact that a certain genotype of the FOXO3 gene is particularly common in the centenarians. Then terms such as longevity gene, aging gene, Greisen- gene or Methuselah gene were used in the press. In September 2008, a U.S. research group had found that the FOXO3 genotype has a significant impact on the life expectancy of a person. Studies in other countries come to the same conclusion .. 2012 Researchers Christian -Albrechts -Universität zu Kiel ( CAU) identifies the FoxO gene as the cause of the potential immortality in freshwater polyps. A gene which is also present in most elderly people, and other animals.

In the non- scientific reporting the facts to FOXO3A is often rendered incorrectly. So every person has this gene in its genome. The Hundred Years' only a specific variation ( genotype) was found that gene that contributes apparently to the increased life of such individuals.