If many adult tissues and organs are continuously replenished by cells derived from stem cells, then why do they show signs of aging? One possibility is that stem cells themselves age and senesce, resulting in a decreased ability to replace worn-out progeny and/or the fact that they pass on aged phenotypes to their progeny.
Missing in this discussion until now is the effect of the cellular and molecular environment on stem cell properties, although the molecular re-programming of epithelial cells into pluripotent stem cells demonstrates the importance of the intracellular environment. Indeed, ample evidence exists showing that intrinsic and extrinsic regulators are inextricably linked in determining stem cell functional properties. Of special current interest is the extracellular stem cell environment, commonly referred to as the stem cell ‘niche’, as originally coined for hematopoietic stem cells in the bone marrow.
The paper starts with a good review of present thinking on the role of stem cells and their niches in aging. It then moves into the interest of the authors in latexin and modulation of the size of stem cell populations:
The qualitative changes in stem cells and the composition of the stem cell population with respect to qualitatively distinct subclasses is an important factor in stem cell aging. We have shown that amongst mouse strains there is a strong correlation between the rate of early hematopoietic progenitor proliferation and mouse lifespan. Moreover, we and others have observed large strain-specific differences in the maintenance of the [hematopoietic stem cell (HSC)] population during aging, thus suggesting that genetic regulation plays an important role in the way aging affects HSCs.
Using forward genetics, we recently identified a protein, latexin, whose differential expression in stem cells accounts for at least part of these differences in young murine hematopoiesis. We have showed that latexin is a negative regulator of stem cell number and acts through at least two mechanisms to modulate stem cell pool size: a) it decreases HSC cell replication and b) it increases HSC apoptosis. Therefore, in the hematopoietic system, and perhaps other organs, latexin influences aging and perhaps lifespan through its action on stem cells.
You'll recall the ongoing debate on decline in stem cell function: is it fewer stem cells, or is it that the stem cells are less active? Evidence exists to support both sides, but with all the work on age-related changes in stem cell niches over the past couple of years, things seemed to be swinging towards less active stem cells as the dominant explanation. Biology is always more complex than we'd like it to be, however, and the debate continues.