Transplantation of Young Bone Marrow into Old Mice Fails to Extend Life Span
Researchers here report on a study of transplantation of bone marrow from young mice to old mice, showing that it improves some measures of immune function, but fails to extend life span. One can compare this with a study from a few years back in which the same approach did in fact extend remaining life span in the old mice. Failures of this nature, where one would expect there to be benefits, are a challenge, as it remains the case that we expect benefits to result if the process was only better optimized in some way. It is hard to draw the line and say that a particular implementation will not work, and why it will not work, without a great deal of further work.
The stem cell theory of aging postulates that stem cells become inefficient at maintaining the original functions of the tissues. We, therefore, hypothesized that transplanting young bone marrow (BM) to old recipients would lead to rejuvenating effects on immunity, followed by improved general health, decreased frailty, and possibly life span extension. We developed a murine model of non-myeloablative heterochronic BM transplantation in which old female BALB/c mice at 14, 16, and 18(19) months of age received altogether 125.1 ± 15.6 million nucleated BM cells from young male donors aged 7-13 weeks. At 21 months, donor chimerism was determined, and the immune system's innate and adaptive arms were analyzed. Mice were then observed for general health and frailty until spontaneous death, when their lifespan, post-mortem examinations, and histopathological changes were recorded.
The results showed that the old mice developed on average 18.7 ± 9.6% donor chimerism in the BM and showed certain improvements in their innate and adaptive arms of the immune system, such as favorable counts of neutrophils in the spleen and BM, central memory Th cells, effector/effector memory Th and Tc cells in the spleen, and B1a and B1b cells in the peritoneal cavity. Borderline enhanced lymphocyte proliferation capacity was also seen. The frailty parameters, pathomorphological results, and life spans did not differ significantly in the transplanted vs. control group of mice. In conclusion, although several favorable effects are obtained in our heterochronic non-myeloablative transplantation model, additional optimization is needed for better rejuvenation effects.
Why didn't they use clones of the old mice as young donor mice?