Transplant of Bone Marrow Cells From Young Mice Modestly Extends Life in Old Mice

In past years researchers have shown that introducing young cells and cell signaling into old individuals via transplant or parabiosis improves some measures of health and reduces some measures of aging. Research here generally focuses on stem cells and the mechanisms by which stem cell activity declines with age: there appears to be a strong signaling component to this decline, presumably a part of the evolved response to accumulating damage in tissues, a way to minimize cancer risk from damaged cells at the cost of failing tissue maintenance and faster aging. So stem cells remain capable of tissue maintenance, but increasingly refrain.

Here researchers are transplanting a significant fraction of bone marrow rather than using the easier approach of blood transfusions to investigate these effects. They find a modest increase in remaining life expectancy for the old mice receiving bone marrow from young donors, but it is worth noting that this was a small group of animals, and a procedure with a high failure rate at this point - this is an early exploratory proof of concept, preliminary to a more rigorous study:

Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SCs). An interesting question is whether donor SCs are capable to prolong the lifespan of an aging organism by tissue renewal. In this work, we investigated the possible use of bone marrow (BM) SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting BM from young 1.5-month-old donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to [about] 25% of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (±0.1) months for the control and experimental groups, respectively, corresponding to a 39 ± 4% increase in the experimental group over the control.

The oldest transplanted animal lived 3 weeks longer than the oldest control animal. However we cannot calculate the maximal lifespan here, since it is, by definition, the mean lifespan of the most long-lived 10% of each group. In our small group, 10% would be less than one mouse. So, the investigation of an influence of BMT on maximal lifespan is the task for future work.

The obtained positive influence of BMT on the mean lifespan in our work is underestimated because of transplantation complications (including the occlusion of vessels) from which, obviously, suffered not only the two mice that died during transplantation and were excluded from the statistics, but also those that survived, though to a lesser degree. We expect a greater difference in lifespan between control and experimental groups by (i) the use of high-quality commercial filters for purification of transplanted material from cell aggregates and (ii) the use of more accurate controls injected with old BM (in this work the control animals did not get the parallel invasive treatment because of the absence of additional 20 months old animals to produce old BM for control transplantation).

Link: http://www.frontiersin.org/Genetics_of_Aging/10.3389/fgene.2013.00144/full

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