To determine how daf-2 functions, Javier Apfeld, a Howard Hughes Medical Institute graduate student in Kenyon's lab, and Kenyon conducted what is known as a "mosaic" analysis, in which they diminished or eliminated daf-2 activity in a wide variety of cell subtypes and observed whether the alteration prompted a corresponding change in the mutated cells themselves or in other cells instead.
What they discovered was that there was not a one-to-one correspondence, or cell "autonomous" relationship, between daf-2 activity and a cell's behavior. Rather, cells responded "cell nonautonomously" to the gene, responding to a secondary message sent from signaling cells that were sensitive to the gene's actions.
"Our findings indicate that daf-2 does not act within each cell to control that cell's fate," said Kenyon.
Moreover, the researchers determined that in animals with intermediate levels of daf-2 signaling activity, the animals became either dauers or adults. Further evidence that there is a secondary mechanism that causes all of the cells in the animal to reach a consensus on whether or not to proceed with the aging process.
"In adult animals, by acting in signaling cells to control the production of a second signal, the daf-2 gene may be able to coordinate the aging process of all the cells in the animal, so that they all age together at the same rate," said Kenyon.
The researchers determined that one of the signaling cell types that daf-2 acts within is nerve cells. It is also possible, said Kenyon, that the gene acts systemically within both neural and nonneural cells, perhaps even in every cell of the animal.
As many biological processes are known to be conserved between C. elegans and
vertebrates, the finding offers possible insight into the way that human aging
is controlled. The possibility is particularly tanta
Contact: Jennifer O'Brien
University of California - San Francisco