Stem cell populations power healing processes; declining effectiveness in this task will clearly cause degeneration, as wear and tear outpaces repair. What is the cause of this decline, and how much does it contribute to frailty, suffering and death versus other classes of age-related cellular damage? Scientists are investigating, but it doesn't even seem clear at this point as to whether biochemical changes or declining numbers of cells are the real culprit - it might be both or neither, or different for differing populations. Much more work is yet to be done, but this, for me, is one of the most exciting areas of stem cell research - how much more healthy life could we gain through repairing or replacing our failing stem cells?

A small collection of abstracts on changes in stem cell populations and effectiveness with age can be found in a recent post in the sci.life-extension group:

The deteriorating in vivo environment is thought to play a major role in reduced stem cell function with age. The capacity of stem cells to support tissue maintenance depends not only on their response to cues from the surrounding niche, but also on their abundance.

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In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 cell diameters thick. Within this narrow zone, a unique microenvironment supports stem cell self renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out of the SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines.

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It is widely believed that cellular senescence is a tumor suppressor mechanism; however, it has not been understood why it is advantageous for organisms to retain mutant cells is a postmitotic state rather than simply eliminating them by apoptosis. It has recently been proposed that the primary role of cellular senescence is in mitotic compartments of fixed size in which spatial considerations dictate that a deleted cell is replaced by a neighboring cell. In these situations, rather than eliminating the neoplastic clone, deletion of mutant cells can paradoxically lead to their increased turnover. If mutant cells become senescent, then the compartment is instead progressively filled by senescent cells until the mutant clone is eliminated. Since most of the genetic alterations responsible for malignancy arise in stem cells, this mechanism may have particular relevance to the stem cell niche. In this article the implications of this hypothesis are examined in detail and related to experimental results. It is further proposed here that blockage of stem cell niches by senescent stem cells may account for some of the functional alterations observed in stem cell compartments at old age.

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Hair graying is the most obvious sign of aging in humans, yet its mechanism is largely unknown. Here, we used melanocyte-tagged transgenic mice and aging human hair follicles to demonstrate that hair graying is caused by defective self-maintenance of melanocyte stem cells.

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We have shown previously that chronically injecting bone-marrow-derived vascular progenitor cells can effect arterial repair. This repair capacity depends on the age of the injected marrow cells, suggesting a progressive decline in progenitor cell function. We hypothesized that the progression of atherosclerosis coincides with the deteriorating repair capacity of the bone marrow.

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Reduced number of circulating endothelial progenitor cells [EPCs] predicts future cardiovascular events ... Reduced levels of circulating EPCs independently predict atherosclerotic disease progression

Technorati tags: aging, stem cell research

Posted by Reason at May 15, 2006 8:55 PM | TrackBack (2)