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Citation
Kao, S.H., Tseng, C.Y., Wan, C.L., Su, Y.H., Hsieh, C.C., Pi, H., Hsu, H.J. (2015). Aging and insulin signaling differentially control normal and tumorous germline stem cells.  Aging Cell 14(1): 25--34.
FlyBase ID
FBrf0227411
Publication Type
Research paper
Abstract

Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging.

PubMed ID
PubMed Central ID
PMC4326914 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Aging Cell
    Title
    Aging Cell
    Publication Year
    2002-
    ISBN/ISSN
    1474-9718 1474-9728
    Data From Reference
    Alleles (9)
    Genes (9)
    Natural transposons (1)
    Experimental Tools (4)
    Transgenic Constructs (4)