By definition, stem cells can self renew indefinitely. But they definitely age, and an active area of research is figuring out how. Working in fruit flies, a team of researchers led by Yukiko Yamashita at the University of Michigan reports a way that organisms balance the risk of tissue degeneration with that of tissue proliferation. Germline stem cells (GSCs) do not divide unless they are set up to do so in the proper orientation.

Long-lived stem cells are able to produce many copies of short-lived specialized cells because of asymmetric divisions. These produce one cell that remains a stem cell and another that commits to many more divisions and further specialization, Within the Drosophila testes, GSCs cluster around a structure called the hub. Physical location determines which cell is which: the inner cell closer to the hub stays a stem cell and the outer differentiates. This balance is maintained by a precise orientation of centrosomes, or structures within cells that help duplicated chromosomes segregate evenly during cell division. By examining Drosophila testes from flies of different ages, the researchers found that GSCs with misoriented centrosomes accumulate with age and that these cells would not divide until these centrosomes became properly aligned. Thus, the more misoriented GSCs, the fewer cell divisions over a period of time, and a decrease in the number of sperm produced. Were such a checkpoint not in place, Yamashita says, the cells could proliferate uncontrollably, a trait characteristic of cancers.

To some extent GSCs with misoriented centrosomes might be as much a symptom as a cause of misorientation. Yamashita and colleagues found that some of these GSCs come from a surprising source: spermatagonia that dedifferentiate back into stem cells rather than going forward to produce sperm. In fact, she believes that this is the major mechanism of replacing GSCs in aging flies.

Leanne Jones of the Salk Institute who also studies spermatogenesis in Drosophila, says that the paper is important for helping explain why GSCs in aging males either stop dividing or progress through the cell cycle slowly. “Yukiko's paper provides a clear mechanism for that,” she says. “What will be interesting is to see if other stem cells that divide with a specific orientation, like epithelial progenitor cells, also arrest when the centrosomes are mis-positioned.” If so, the next questions would be whether mis-positioning increases with age, and whether the same checkpoint mechanism is used for different sorts of stem cells.