Stem Cell Aging Is Controlled Both Intrinsically and Extrinsically in the Drosophila Ovary

Abstract

It is widely postulated that tissue aging could be, at least partially, caused by reduction of stem cell number, activity, or both. However, the mechanisms of controlling stem cell aging remain largely a mystery. Here, we use Drosophila ovarian germline stem cells (GSCs) as a model to demonstrate that age-dependent decline in the functions of stem cells and their niche contributes to overall stem cell aging. BMP signaling activity from the niche significantly decreases with age, and increasing BMP signaling can prolong GSC life span and promote their proliferation. In addition, the age-dependent E-cadherin decline in the stem cell-niche junction also contributes to stem cell aging. Finally, overexpression of SOD, an enzyme that helps eliminate free oxygen species, in either GSCs or their niche alone can prolong GSC life span and increase GSC proliferation. Therefore, this study demonstrates that stem cell aging is controlled extrinsically and intrinsically in the Drosophila ovary.

Age‐related changes of germline stem cell activity, niche signaling activity and egg production in Drosophila

“…These results are consistent with the notion that reduced production of niche signals such as BMP and Hh contribute to decreased activation within GSC, and consequently to the decline in net GSC activity. Similar conclusions are reported in two recent Drosophila studies (Boyle et al, 2007;Pan et al, 2007). In the male GSC niche, the expression of unpaired (upd ), a key self-renewal factor, declines with age, contributing to the progressive loss of GSC proliferation (Boyle et al, 2007).…”

“…In the male GSC niche, the expression of unpaired (upd ), a key self-renewal factor, declines with age, contributing to the progressive loss of GSC proliferation (Boyle et al, 2007). In the female GSC niche, Pan et al (2007) also demonstrate that BMP signaling activity from the niche significantly decreases with age that contributes GSC aging. Together, these findings suggest that the niche itself is subject to senescence, with the decline of stem cells following as a consequence.…”

piRNA-mediated transgenerational inheritance of an acquired trait

“…A priori, aging could affect the physiology of any ovarian tissue. Even germinal stem cells (GSCs) were reported to age and die after a number of asymmetric divisions (Xie and Spradling 2000;Pan et al 2007) generating one GSC and one cystoblast (i.e., the differentiated precursor of the future egg) (Spradling et al 2001).…”

Cell intrinsic and extrinsic mechanisms of stem cell aging depend on telomere status

“…Emerging data suggest that systemically acting factors and alterations in cell-to-cell contact in stem niches impinge on stem cell aging (Boyle et al, 2007;Pan et al, 2007;Zhao et al, 2008) . The relative contribution of telomere dysfunction to these mechanisms of stem cell aging remains yet to be defined across different organ systems.…”