Slow sensing ages stem cells

Adult stem cells become slower at dividing as they age because they get less efficient at sensing their microenvironment, according to a study to be published in Nature tomorrow. The findings suggest a mechanism to explain why production of adult stem cells such as sperm drops as an organism gets older. "I think this is a fantastic piece of work that begins to explain" how adult stem cells age, said linkurl:Leanne Jones,;http://www-biology.ucsd.edu/faculty/jonesl.html a stem cell biologist at

Written byJennifer Evans

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Adult stem cells become slower at dividing as they age because they get less efficient at sensing their microenvironment, according to a study to be published in Nature tomorrow. The findings suggest a mechanism to explain why production of adult stem cells such as sperm drops as an organism gets older. "I think this is a fantastic piece of work that begins to explain" how adult stem cells age, said linkurl:Leanne Jones,;http://www-biology.ucsd.edu/faculty/jonesl.html a stem cell biologist at the Salk Institute, who was not involved in the study. Adult stem cells divide linkurl:asymmetrically,;http://www.the-scientist.com/article/display/54197/ yielding one stem cell and one specialized daughter cell. But over time, they develop delays in their cell cycle, a factor thought to be linked to tissue aging. The stem cell niche, or microenvironment, helps to maintain stem cell identity by signaling for cell division to be turned on and off, said linkurl:Yukiko Yamashita,;http://www.lsi.umich.edu/facultyresearch/labs/yamashita a stem cell scientist at the University of Michigan and lead author of study. In linkurl:previous work,;http://www.the-scientist.com/article/display/21585/ Yamashita found that the position of centrosomes -- the organizing centers for microtubules during cell division -- governed asymmetric cell division. So she hypothesized centrosome orientation could also affect cell cycle activity. "We knew that centrosome orientation appears to be important [in asymmetric division]," Yamashita said. "What we didn't know was whether or not the stem cell thinks [centrosome orientation] is important." To find out, Yamashita's team tagged proteins with linkurl:GFP;http://www.the-scientist.com/blog/display/55077/ to track the movement of centrosomes in germline stem cells (GSCs) in the testes of live Drosophila males ranging from "early puberty to middle age." They then visualized GSC niche cells, GSCs and centrosomes using immunoflorescence staining. The older the flies, the greater the number of GSCs that had misoriented centrosomes in relation to the GSC niche, the researchers found. But the next stage in the cell cycle -- spindle formation -- was absent, suggesting that the cells suspended the process of cell division in response to misoriented centrosomes. The group also observed that cell division resumed as soon as centrosomes were correctly orientated. The findings show "centrosomes are the proximal reason whether a stem cell goes through mitosis or not," Yamashita said. The centrosomes appear to be acting essentially as a sensors for the cell's orientation, she explained. "What's nice about this work is it shows that centrosome positioning is 'off' in older stem cells, but the cells always recover," said Jones. Yamashita said her findings suggest the centrosome has to be in the 'right place' before cell cycle resumes. "The delay in GSC cell cycle in aging flies as a result of centrosome misorientation suggests a mechanism for the decline in sperm production previously indicated in studies of aging animals," Jones said. In the future, Yamashita said her group hopes to identify the checkpoint components that are halting cellular division in misoriented stem cells.