More Ways For Aging Stem Cells To Go Awry

There closer scientists look, the more ways they find for our aging stem cells to fail. Since stem cells are necessary to repair ongoing wear in our tissues, their loss of function is an important contributer to degenerative aging. My attention was drawn today to a novel discovery: a malfunction in the mechanisms of cell replication and differentiation that doesn't look much like any of the more familiar ways in which cells fail with age.

Asymmetric division of adult stem cells generates one self-renewing stem cell and one differentiating cell, thereby maintaining tissue homeostasis. A decline in stem cell function has been proposed to contribute to tissue ageing, although the underlying mechanism is poorly understood. Here we show that changes in the stem cell orientation with respect to the niche during ageing contribute to the decline in spermatogenesis in the male germ line of Drosophila.

Throughout the cell cycle, centrosomes in germline stem cells (GSCs) are oriented within their niche and this ensures asymmetric division. We found that GSCs containing misoriented centrosomes accumulate with age and that these GSCs are arrested or delayed in the cell cycle. The cell cycle arrest is transient, and GSCs appear to re-enter the cell cycle on correction of centrosome orientation.

On the basis of these findings, we propose that cell cycle arrest associated with centrosome misorientation functions as a mechanism to ensure asymmetric stem cell division, and that the inability of stem cells to maintain correct orientation during ageing contributes to the decline in spermatogenesis. We also show that some of the misoriented GSCs probably originate from dedifferentiation of spermatogonia.

So, translated to English from the Scientese: there is a fiddly, complex structure within stem cells upon which their most vital function - the generation of new cells - depends. This structure, the centrosome, only works when in the right relationship with the surrounding stem cell niche. As flies get older, more and more of stem cells fall out of this correct relationship.

Interestingly, we already know that the stem cell niche, the tissue in which stem cells are sustained, is important in the decline of stem cell function with aging - it's wrong to think of stem cells in isolation. The real mechanism in your body consists of an entire stem cell population plus the signaling and support mechanisms of the niche in which they are sustained. It's all connected.

This new finding will no doubt have scientists scratching their heads and digging in deeper. Are misaligned centrosomes a cause or effect - a symptom of other cellular damage, or a stand-alone form of decline? It will be interesting to find out.


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