Fight Aging!

It is my estimate that reversing stem cell aging is not likely to arrive first in the list of possible near term advances in rejuvenation biotechnology. It is a hard problem. In fact it will only arrive at all because the stem cell research community is very large, well-funded, and energetic, and because those researchers have to solve the problem of diminished stem cell activity with age in order to effectively deliver therapies. Most of the foreseeable uses of stem cell-based regenerative medicine involve treating degenerative age-related conditions, but only if an age-damaged metabolism can be stopped from persistently sabotaging the desired end result of treatment.

The accumulating knowledge of recent years suggests that stem cell aging is very complicated. It may occur in quite different ways in the scores of different stem cell populations, not all of which are presently well understood. It may depend on the ecology of stem cell niches, which are themselves more complicated entities than the stem cells they shelter. The different niches supporting different stem cells can diverge greatly in form and function as well.

For example, if you look back at work on FGF signaling in the stem cell niche from last year, you might note that it involves satellite cells in muscle - one of the better-studied stem cell populations - but there is no reason to expect the findings to be repeated in any other stem cell population. There is no necessary reason for the mechanisms that lead to the similar end result of declining stem cell function to be the same in different tissue types; they only had to evolve to do roughly the same thing, not work the same way.

As another example of the complexities of stem cell aging, you might look at this open access paper:

http://impactaging.com/papers/v5/n1/full/100530.html

The causes underlying aging remain poorly understood. One prominent theory is that a decrease in stem cell function over time plays a significant role in tissue aging, which ultimately manifests at the organismal level. This could be through cell-intrinsic alterations in the stem cell pool, cell-extrinsic changes affecting stem cell function, or a combination of both. However, the noticeable exception to this idea was the fact that the skin, which contains some of the most amenable and best-studied stem cell populations and which progressively loses its ability to maintain tissue homeostasis with age, had no previously documented age-associated changes in stem cell function.

Recent work has now uncovered a subset of epidermal stem cells in the hair follicle bulge that undergoes significant changes during normal aging. Using [a well characterized mouse model] to study and isolate stem cells during aging, this study identified increases in stem cell number but decreases in functional capacity of this population over time, and advances the hypothesis that broader age-associated stem cell alterations contribute significantly to skin aging.

In light of this finding, it is important to keep in mind the diverse heterogeneity of stem cell populations present in the mammalian epidermis. This heterogeneity not only applies to functionality, but also manifests in a compartmentalized fashion, with discrete sets of stem cells occupying distinct anatomical niches, including the interfollicular epidermis (IFE), the hair follicle (HF) bulge, and the isthmus region at the interface of the IFE and HF. It is this heterogeneity, in both location and function that likely masked previous attempts to identify aging stem cell changes in skin

Even skin is very complex, with many populations of distinct stem cells. The hair follicle stem cells noted above are unusual given that there are apparently more of them with age. That is a contrast with studies of other stem cell types: much of the debate over satellite cells in muscle was whether the number of cells was diminishing or just their capacity to act, for example. So what does this all mean? It means that it is a good thing that the stem cell research establishment is large and growing, as it needs to be large and growing in order to have a good chance of success over the next few decades in the issue of stem cell aging.