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Aging Cell

Title:		Aging and insulin signaling differentially control normal and tumorous germline stem cells
Author(s):		Kao SH; Tseng CY; Wan CL; Su YH; Hsieh CC; Pi H; Hsu HJ;
Address:		"Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, 11529, Taiwan"
Journal Title:		Aging Cell
Year:		2015
Volume:		20141203
Issue:		1
Page Number:		25 - 34
DOI:		10.1111/acel.12288
ISSN/ISBN:		1474-9726 (Electronic) 1474-9718 (Print) 1474-9718 (Linking)
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"
Keywords:		Aging/*metabolism Animals Biomarkers/metabolism Cell Count Cell Proliferation DNA/metabolism DNA Damage Drosophila melanogaster/*cytology/*metabolism Female Flow Cytometry G1 Phase Germ Cells/*pathology Insulin/*metabolism Male Neoplastic Stem Cells/*meta;
Notes:		"MedlineKao, Shih-Han Tseng, Chen-Yuan Wan, Chih-Ling Su, Yu-Han Hsieh, Chang-Che Pi, Haiwei Hsu, Hwei-Jan eng Research Support, Non-U.S. Gov't England 2014/12/04 Aging Cell. 2015 Feb; 14(1):25-34. doi: 10.1111/acel.12288. Epub 2014 Dec 3"