Stem Cells and the Aging Hematopoietic System

Overview

Journal Curr Opin Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2010 Jul 24

PMID 20650622

Citations 96

Authors

Isabel Beerman

William J Maloney

Irving L Weissmann

Derrick J Rossi

Affiliations

Soon will be listed here.

Abstract

Advancing age is accompanied by a number of clinically significant conditions arising in the hematopoietic system that include: diminution and decreased competence of the adaptive immune system, elevated incidence of certain autoimmune diseases, increased hematological malignancies, and elevated incidence of age-associated anemia. As with most tissues, the aged hematopoietic system also exhibits a reduced capacity to regenerate and return to normal homeostasis after injury or stress. Evidence suggests age-dependent functional alterations within the hematopoietic stem cell compartment significantly contribute to many of these pathophysiologies. Recent developments have shed light on how aging of the hematopoietic stem cell compartment contributes to hematopoietic decline through diverse mechanisms.

Citing Articles

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Age-associated imbalance in immune cell regeneration varies across individuals and arises from a distinct subset of stem cells.

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DNA methylation drives hematopoietic stem cell aging phenotypes after proliferative stress.

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References

Liang Y, van Zant G, Szilvassy S . Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood. 2005; 106(4):1479-87. PMC: 1895199. DOI: 10.1182/blood-2004-11-4282. View

Silverman L, Demakos E, Peterson B, Kornblith A, Holland J, Odchimar-Reissig R . Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002; 20(10):2429-40. DOI: 10.1200/JCO.2002.04.117. View

Guerrettaz L, Johnson S, Cambier J . Acquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging. Proc Natl Acad Sci U S A. 2008; 105(33):11898-902. PMC: 2515225. DOI: 10.1073/pnas.0805498105. View

Michallet M, Philip T, Philip I, Godinot H, Sebban C, Salles G . Transplantation with selected autologous peripheral blood CD34+Thy1+ hematopoietic stem cells (HSCs) in multiple myeloma: impact of HSC dose on engraftment, safety, and immune reconstitution. Exp Hematol. 2000; 28(7):858-70. DOI: 10.1016/s0301-472x(00)00169-7. View

Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman I, Bryder D . Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A. 2010; 107(12):5465-70. PMC: 2851806. DOI: 10.1073/pnas.1000834107. View

Dykstra B, Kent D, Bowie M, McCaffrey L, Hamilton M, Lyons K . Long-term propagation of distinct hematopoietic differentiation programs in vivo. Cell Stem Cell. 2008; 1(2):218-29. DOI: 10.1016/j.stem.2007.05.015. View

Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G . Development of functional human blood and immune systems in NOD/SCID/IL2 receptor {gamma} chain(null) mice. Blood. 2005; 106(5):1565-73. PMC: 1895228. DOI: 10.1182/blood-2005-02-0516. View

Linton P, Dorshkind K . Age-related changes in lymphocyte development and function. Nat Immunol. 2004; 5(2):133-9. DOI: 10.1038/ni1033. View

Tsaknaridis L, Spencer L, Culbertson N, Hicks K, LaTocha D, Chou Y . Functional assay for human CD4+CD25+ Treg cells reveals an age-dependent loss of suppressive activity. J Neurosci Res. 2003; 74(2):296-308. DOI: 10.1002/jnr.10766. View

10.

Nijnik A, Woodbine L, Marchetti C, Dawson S, Lambe T, Liu C . DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 2007; 447(7145):686-90. DOI: 10.1038/nature05875. View

11.

Signer R, Montecino-Rodriguez E, Witte O, McLaughlin J, Dorshkind K . Age-related defects in B lymphopoiesis underlie the myeloid dominance of adult leukemia. Blood. 2007; 110(6):1831-9. PMC: 1976345. DOI: 10.1182/blood-2007-01-069401. View

12.

Morita Y, Ema H, Nakauchi H . Heterogeneity and hierarchy within the most primitive hematopoietic stem cell compartment. J Exp Med. 2010; 207(6):1173-82. PMC: 2882827. DOI: 10.1084/jem.20091318. View

13.

Park Y, Gerson S . DNA repair defects in stem cell function and aging. Annu Rev Med. 2005; 56:495-508. DOI: 10.1146/annurev.med.56.082103.104546. View

14.

Muller-Sieburg C, Cho R, Karlsson L, Huang J, Sieburg H . Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness. Blood. 2004; 103(11):4111-8. DOI: 10.1182/blood-2003-10-3448. View

15.

Rossi D, Jamieson C, Weissman I . Stems cells and the pathways to aging and cancer. Cell. 2008; 132(4):681-96. DOI: 10.1016/j.cell.2008.01.036. View

16.

Morrison S, Wandycz A, Akashi K, Globerson A, Weissman I . The aging of hematopoietic stem cells. Nat Med. 1996; 2(9):1011-6. DOI: 10.1038/nm0996-1011. View

17.

Rossi D, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman I . Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 2007; 447(7145):725-9. DOI: 10.1038/nature05862. View

18.

Harrison D . Mouse erythropoietic stem cell lines function normally 100 months: loss related to number of transplantations. Mech Ageing Dev. 1979; 9(5-6):427-33. DOI: 10.1016/0047-6374(79)90083-6. View

19.

Sudo K, Ema H, Morita Y, Nakauchi H . Age-associated characteristics of murine hematopoietic stem cells. J Exp Med. 2000; 192(9):1273-80. PMC: 2193349. DOI: 10.1084/jem.192.9.1273. View

20.

Ogawa T, Kitagawa M, Hirokawa K . Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages. Mech Ageing Dev. 2000; 117(1-3):57-68. DOI: 10.1016/s0047-6374(00)00137-8. View