Experiments based on exposing old tissue to a young environment, and vice versa, have been gaining much more attention in recent years. The most common are the heterochronic parabiosis studies in which the circulatory systems of an old and a young individual are linked, with the result that the older individual benefits in a modest reduction in many measures of age-related decline, such as stem cell activity. This has led research groups to focus on the effects of signal molecules in the bloodstream as a proximate cause for some age-related changes in biochemistry. There are many other approaches to mixing old and young biochemistries, however, and in this open access paper the authors report on the results of taking an easily transplanted structure within skin, the hair follicle, and moving it between old and young individuals:
Recently, parabiosis experiments pairing old and young mice have suggested that some features of aging organs in old mice, in particular stem cells, can be reversed by factors in blood of young mice, including brain, spinal cord, and heart. The hair follicle, which cycles through telogen (resting), anagen (growing), and catagen (regression) throughout the life of mammals, undergoes obvious age-related changes including hair loss. The hair follicle contains hair-follicle-associated pluripotent (HAP) stem cells, which may also deteriorate during aging. Instead of using complex parabiosis surgery, we used hair-follicle subcutaneous transplantation in order to determine if the hair follicle, including its ability to produce hair shafts, and its HAP stem cells, can be rejuvenated.
We transplanted young hair follicles subcutaneously into both young and old nude mice. We also transplanted old hair follicles into young and old nude mice. In young nude mice, the transplanted young hair follicles started to establish blood vessel connections and hair shafts began to grow by week 2. The old hair follicles transplanted to young nude mice also established blood vessel connections by week 2. The growth rate of old hair follicles in young nude mice was somewhat slower than young hair follicles. In contrast, in old nude mice, both transplanted young and old hair follicles failed to regrow extensive hair shafts. At week 2 and week 4, both the young and old transplanted hair follicles had less blood vessel connections with old host mice, in contrast to blood vessel connections in young mice.
Therefore, our results showed that both young and old hair follicles can regrow extensive hair shafts when transplanted to young nude mice, while neither young nor old hair follicles can regrow extensive hair shafts when transplanted to old nude mice. These results suggest that young nude mice can provide a more suitable environment to subcutaneously-transplanted hair follicles, both young and old, than old nude host mice. These results also suggest a large influence of the host nude on the donated hair follicles, due to the fact that both young and old hair follicles fail to regrow long hair shafts in old host mice. Old hair follicles had the capability to regrow long hair shafts when transplanted to young host mice, suggesting that old hair follicles can be rejuvenated by young host mice. In young nude host mice, HAP stem cells in the transplanted follicle were active throughout the 8-week experimental period as can be seen by their expression of nestin-driven green fluorescent protein (ND-GFP). ND-GFP expressing cells were widely distributed in both young and old hair follicles transplanted to young host nude mice. HAP stem cells were located in various areas of the follicle, including the follicle sensory nerve, hair matrix bulb and outer-root sheath. HAP stem cells surrounded the hair bulb at week 8 suggesting their role in hair-shaft regrowth. In old hair follicles of old nude mice, most of the ND-GFP expressing cells were located in the attached sensory nerves but not in the center of the hair follicle as they were in old follicles transplanted to old mice. Thus the subcutaneous environment has a strong influence on the HAP stem cells of young and old hair follicles.