Here, researchers report on the results of transplanting cells from young bone marrow into old mice. The bone marrow came from genetically identical young mice, so there was no risk of rejection. Unlike the usual process for bone marrow transplants, there was no ablative chemotherapy to kill existing stem cells. This strategy led to a high degree of integration of young stem cells into the aged bone marrow, with cells of young origin making up a quarter of the bone marrow by the end of the study. This sizable integration is likely because old bone marrow has much smaller active stem cell populations, and thus their comparatively feeble efforts to produce daughter cells were outpaced by the activities of the transplanted cells.
As a result of this procedure, the maximum life span of the aged mice population was extended by nearly 30%. We can envisage many mechanisms by which this improvement can occur, such as greater production of immune cells, leading to a more active and competent immune system, or improved systemic signaling that may affect all organs, not just the bone marrow. The authors of the paper use these results to argue for the adoption of a similar therapy for old human patients, bone marrow transplantation without the ablative chemotherapy that characterizes its usual use in cancer patients, in order to achieve some degree of rejuvenation of tissue and immune system.
Increase in maximum lifespan (MLS) is the most significant indicator of hitting the basic mechanisms of aging, in particular, regarding age-related loss of stem cells and cell damage accumulation. In this study, a significant (30%) increase in maximum lifespan of mice was found after nonablative transplantation of 100 million nucleated bone marrow (BM) cells from young donors, initiated at the age that is equivalent to 75 years for humans. Moreover, rejuvenation was accompanied by a high degree of BM chimerism for the nonablative approach. Six months after the transplantation, 28% of recipients' BM cells were of donor origin. The relatively high chimerism efficiency that we found is most likely due to the advanced age of our recipients having a depleted BM pool.
In addition to the higher incorporation rates, there are more reasons why the nonablative setting is preferable for old recipients. These are lesser risks of infections and of graft-vs-host disease, threatening to ablated patients, while graft rejection by nonablated recipients is less probable in the elderly than at a younger age because of naturally weaker immune system in the elderly. Even in the absence of histocompatibility, when allogeneic BM was used in a nonablative experiment instead of syngeneic BM, no lifespan shortening of the experimental group was observed.
Obviously, at an old age the immune system is already too passive to reject donor BM, but it still efficiently suppresses infection and graft-vs.-host reaction, which makes it unnecessary and undesirable to use ablative conditioning in the elderly. On the bases of the above and our data, we advocate a more rapid implementation of nonablative stem cell transplantation into the clinic not only for pathology treatment, but also for rejuvenation.