Abstract
Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16-18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.
Highlights
Bone marrow derived stem cells (BMDSCs) were initially studied for their role in hematopoiesis but in the last 15-20 years the role of these stem cells in regeneration and repair of other tissues and in aging has been an active area of research
To test the hypothesis that BMDSCs contribute to the stem cell population of other organs and in this way restore tissue stem cells and delay organismal aging, we studied the effect of bone marrow transplantation using young and old donors and p53-based early aging mouse models
To test the hypothesis that premature aging could be induced in wild-type recipients of +/m bone marrow, we transplanted four-week old lethally irradiated wild-type female C57Bl/6 mice with 2 X 106 BM from 8 week old p53+/m male C57Bl/6 mice and a control group with 8 week old wild-type male bone marrow (n=20/group)
Summary
Bone marrow derived stem cells (BMDSCs) were initially studied for their role in hematopoiesis but in the last 15-20 years the role of these stem cells in regeneration and repair of other tissues and in aging has been an active area of research. We theorized that if BMDSCs play a role in the aging process, transplantation of BM from early aging donors into lethally irradiated wild-type recipients should induce premature aging, and transplantation of bone marrow (BM) from young wild-type donors should extend the lifespan of recipients with early aging phenotypes. In these studies, control groups of C57BL/6 mice receiving young wild-type bone marrow did not survive significantly longer than mice receiving old wild type bone marrow. In this study we found that the ICR strain of mice www.impactaging.com
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