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. 1976 Nov 2;144(5):1204–1213. doi: 10.1084/jem.144.5.1204

Decline in the growth potential of spleen-colonizing bone marrow stem cells of long-lived aging mice

PMCID: PMC2190459  PMID: 993725

Abstract

The growth capacity of femoral bone marrow stem cells from young and old long-lived mice was assessed in the spleen of X-irradiated young and old syngeneic recpients by determining: (a) the number of stem cells colonizing the spleen, (b) the rate of incorporation of 125I- labeled iododeoxyuridine by proliferating colony cells, and (c) the number of cells present in the largest colonies at the end of the growth phase.We found that the growth capacity of stem cells declined with age. We further found that the spleen-seeking and spleen colony growth capacities of old stem cells remained characteristically old even after they were allowed to self-replicate in the bone marrow of young recipients for an extended period of time. On the other hand, the spleen colony growth capacity of young stem cells could be reduced by allowing them to self-replicate in old recipients. These results suggest that the growth capacity of old stem cells is an intrinsic characteristic which cannot be readily altered, but that of young stem cells can be aged in an accelerated manner by allowing them to self- replicate in old recipients. An additional reduction was noted in the frequency of both young and old stem cells colonizing the spleen of old recipients and in the cell density of the largest colonies produced. These results indicate that factors extrinsic to the stem cells are also responsible for the decline with age in their spleen colony growth capacity.Thus, the growth capacity of old stem cells in old recipients could be as low as 10% that of young stem cells in young recipients.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albright J. F., Makinodan T. Growth and senescence of antibody-forming cells. J Cell Physiol. 1966 Jun;67(3 Suppl):185+–185+. doi: 10.1002/jcp.1040670415. [DOI] [PubMed] [Google Scholar]
  2. BECKER A. J., McCULLOCH E. A., TILL J. E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature. 1963 Feb 2;197:452–454. doi: 10.1038/197452a0. [DOI] [PubMed] [Google Scholar]
  3. CUDKOWICZ G., BENNETT M., SHEARER G. M. PLURIPOTENT STEM CELL FUNCTION OF THE MOUSE MARROW "LYMPHOCYTE". Science. 1964 May 15;144(3620):866–868. doi: 10.1126/science.144.3620.866. [DOI] [PubMed] [Google Scholar]
  4. CUDKOWICZ G., UPTON A. C., SHEARER G. M., HUGHES W. L. LYMPHOCYTE CONTENT AND PROLIFERATIVE CAPACITY OF SERIALLY TRANSPLANTED MOUSE BONE MARROW. Nature. 1964 Jan 11;201:165–167. doi: 10.1038/201165a0. [DOI] [PubMed] [Google Scholar]
  5. Chen M. G. Age-related changes in hematopoietic stem cell populations of a long-lived hybrid mouse. J Cell Physiol. 1971 Oct;78(2):225–232. doi: 10.1002/jcp.1040780209. [DOI] [PubMed] [Google Scholar]
  6. Chino F., Makinodan T., Lever W. E., Peterson W. J. The immune systems of mice reared in clean and in dirty conventional laboratory farms. I. Life expectancy and pathology of mice with long life-spans. J Gerontol. 1971 Oct;26(4):497–507. doi: 10.1093/geronj/26.4.497. [DOI] [PubMed] [Google Scholar]
  7. Curry J. L., Trentin J. J. Hemopoietic spleen colony studies. I. Growth and differentiation. Dev Biol. 1967 May;15(5):395–413. doi: 10.1016/0012-1606(67)90034-6. [DOI] [PubMed] [Google Scholar]
  8. Farrar J. J., Loughman B. E., Nordin A. A. Lymphopoietic potential of bone marrow cells from aged mice: comparison of the cellular constituents of bone marrow from young and aged mice. J Immunol. 1974 Mar;112(3):1244–1249. [PubMed] [Google Scholar]
  9. Goodman S. A., Makinodan T. Effect of age on cell-mediated immunity in long-lived mice. Clin Exp Immunol. 1975 Mar;19(3):533–542. [PMC free article] [PubMed] [Google Scholar]
  10. HUGHES W. L., COMMERFORD S. L., GITLIN D., KRUEGER R. C., SCHULTZE B., SHAH V., REILLY P. DEOXYRIBONUCLEIC ACID METABOLISM IN VIVO: I. CELL PROLIFERATION AND DEATH AS MEASURED BY INCORPORATION AND ELIMINATION OF IODODEOXYURIDINE. Fed Proc. 1964 May-Jun;23:640–648. [PubMed] [Google Scholar]
  11. Harrison D. E., Doubleday J. W. Normal function of immunologic stem cells from aged mice. J Immunol. 1975 Apr;114(4):1314–1317. [PubMed] [Google Scholar]
  12. Harrison D. E. Normal function of transplanted marrow cell lines from aged mice. J Gerontol. 1975 May;30(3):279–285. doi: 10.1093/geronj/30.3.279. [DOI] [PubMed] [Google Scholar]
  13. Hayflick L. Current theories of biological aging. Fed Proc. 1975 Jan;34(1):9–13. [PubMed] [Google Scholar]
  14. Lajtha L. G., Schofield R. Regulation of stem cell renewal and differentiation: possible significance in aging. Adv Gerontol Res. 1971;3:131–146. [PubMed] [Google Scholar]
  15. Micklem H. S., Ford C. E., Evans E. P., Ogden D. A., Papworth D. S. Competitive in vivo proliferation of foetal and adult haematopoietic cells in lethally irradiated mice. J Cell Physiol. 1972 Apr;79(2):293–298. doi: 10.1002/jcp.1040790214. [DOI] [PubMed] [Google Scholar]
  16. Nowell P. C., Hirsch B. E., Fox D. H., Wilson D. B. Evidence for the existence of multipotential lympho-hematopoietic stem cells in adult rat. J Cell Physiol. 1970 Apr;75(2):151–158. doi: 10.1002/jcp.1040750203. [DOI] [PubMed] [Google Scholar]
  17. Price G. B., Makinodan T. Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies. J Immunol. 1972 Feb;108(2):403–412. [PubMed] [Google Scholar]
  18. Price G. B., Makinodan T. Immunologic deficiencies in senescence. II. Characterization of extrinsic deficiencies. J Immunol. 1972 Feb;108(2):413–417. [PubMed] [Google Scholar]
  19. SIMINOVITCH L., TILL J. E., MCCULLOCH E. A. DECLINE IN COLONY-FORMING ABILITY OF MARROW CELLS SUBJECTED TO SERIAL TRANSPLANTATION INTO IRRADIATED MICE. J Cell Physiol. 1964 Aug;64:23–31. doi: 10.1002/jcp.1030640104. [DOI] [PubMed] [Google Scholar]
  20. TILL J. E., McCULLOCH E. A. A direct measurement of the radiation sensitivity of normal mouse bone marrow cells. Radiat Res. 1961 Feb;14:213–222. [PubMed] [Google Scholar]
  21. Wu A. M., Till J. E., Siminovitch L., McCulloch E. A. A cytological study of the capacity for differentiation of normal hemopoietic colony-forming cells. J Cell Physiol. 1967 Apr;69(2):177–184. doi: 10.1002/jcp.1040690208. [DOI] [PubMed] [Google Scholar]

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