Two papers, published back-to-back last week in Cell Stem Cell, address the mechanisms of aging in the Drosophila gonad, specifically germ line stem cells (GSCs). One group studied the testis, the other the ovary, but both come to similar conclusions: Changes in the stem cell niche — i.e., the local tissue microenvironment that surrounds and supports stem cells — are critical to the rate of functional aging.

Yin: In the (ordinally) first of the two papers, Pan et al. demonstrate that BMP and E-cadherin signaling from ovarian niche cells declines with age, and that boosting the level of BMP secreted by niche cells can slow ovarian GSC aging. The authors also show that expression of the antioxidant enzyme SOD, either in niche cells or in stem cells themselves, also slows the rate of functional decline. I find this result less surprising, as oxidation is widely thought to influence aging, though it is worth keeping in mind that stem cell-intrinsic factors are also relevant to aging (for an example in human stem cells, see our earlier post Sucking the life out of marrow).

Yang: Switching gears (and genders) to focus on the testis, Boyle et al. (from the lab of rising star Leanne Jones) uncover a similar story: In the aging testis, niche cells (clustered at one tip of the organ in a region called the “hub”) express lower levels of DE-cadherin and a self-renewal signal called unpaired. As these molecules decline, the number of GSCs decreases, lowering the overall rate of spermatogenesis. As in Pan et al., artificially providing one of the lost molecules (this time, unpaired) rescued the age-related decline in stem cell number.

All fine and good for (unpaired-transgenic) flies, but why should we mammals be interested? Declines in stem cell number and proliferation capacity are thought to be associated with aging and age-related pathology. Stem cell therapy (sometimes envisioned as a simple matter of procuring stem cells of the appropriate lineage and immunological flavor and introducing them into a sick or decrepit body, where they will doubtless know what to do while politely refraining from causing cancer) has been touted as a remedy for disease or even for aging itself.

But here’s a wrinkle, pun not intended: These papers add to the growing body of evidence that stem cells don’t fare well in aged niches. In other words, the stable introduction stem cells into patients will become more difficult as a function of the recipients’ age; since it’s a question of capacity rather than efficiency, the problem can’t be solved by adding more stem cells.

Clinically, this means that in addition to finding immunologically compatible stem cells for each patient and optimizing the conditions for transplantation, we may need to engineer the niche itself in order to cajole aged tissues into accepting a new batch of stem cells — and this will be very hard. We are much better at manipulating cells outside the body and re-introducing them than we are at making genetic changes to particular cells inside a specific tissue architecture while they remain inside the body — and by “much better” I mean that at present we can do the former sometimes and the latter not at all.

Perhaps a better approach would be to make the stem cells less sensitive to the cues they receive from the niche? Yes, that would be nice: immortal cells, freed from requirements for context-specific pro-growth and anti-apoptotic factors, free in the body to do as they pleased…oh, wait.