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Stem Cell Aging Is Controlled Both Intrinsically and Extrinsically in the Drosophila Ovary
Lei Pan,1,2 Shuyi Chen,1,3 Changjiang Weng,1 Gerald Call,1,5 Dongxiao Zhu,1,4 Hong Tang,2 Nian Zhang,1 and Ting Xie1,3,
1 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA
2 Center for Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Road, Beijing 100101, China
3 Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
4 Department of Biostatistics, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
5 Department of Pharmacology, Arizona College of Osteopathic Medicine, Midwestern University, 19555 North 59th Avenue, Glendale, AZ 85308, USA
Corresponding author
Ting Xie
Summary
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.
