Forkhead transcription factors and age-related DAF-16 studies

Orthologues are one of the classes of homologue genes. They occur in different species, but are linked by a common ancestral pathway. During evolution, they retain the same original function, irrespective of the species. Among the orthologues covered on our antibody database are those of the Forkhead transcription factor (FOX) superfamily of proteins.

Forkhead box O-class (FOXO) transcription factors are mammalian homologues of DAF-16, a protein which is known to be a lifespan regulator of the nematode worm Caenorhabditis elegans. Among the transcription factors we at Novus Biologicals have in our antibody catalogue are FOXO1, FOXO3a and FOXO4. In mammals they are linked to apoptosis, DNA repair, response to oxidative stress, metabolism and the regulation of the cell cycle.

FOX01a, 03a and 04 have been linked to tumourigenesis, having first been identified at human tumour chromosomal breaks. Antibody studies showed them to be targets of the PI3K/PKB pathway, which is known to play a part in oncogenesis. The discovery that DAF-16 was a target for PKB in C.elegans proved it to be a homologue of FOXO1a, FOXO3a and FOX04, which are similar in structure to DAF-16 and are its mammalian equivalent.

The FOX0 genes are known to play a part in age-related conditions such as cancer and diabetes. Recently, researchers at the University of Massachusetts Medical School discovered a new DAF-16 isoform, DAF-16d/f, which together with the isoform DAF-16a was shown to regulate longevity in C.elegans. DAF-16 is part of the insulin signalling pathway, and is at the centre of a complex network of protein pathways.

By performing anti-aging antibody studies on a relatively simple animal with genetic links to humans, it is hoped to uncover some of the causes of human age-related diseases.

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