Stem cell ageing: Does it happen and can we intervene?

Expert Reviews in Molecular Medicine

Volumn 9, Issue 31, 2007, Pages 1-20

  Bellantuono, Ilaria ^a   Keith, W Nicol ^b  

^a UNIVERSITY OF SHEFFIELD   (United Kingdom)

^b UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; PROTEIN P21; PROTEIN P27; VALPROIC ACID;

ALZHEIMER DISEASE; ARTICLE; CD34 SELECTION; CELL AGING; CELL CYCLE G1 PHASE; CELL DIVISION; CELL FUNCTION; CELL PROLIFERATION; CELL REGENERATION; CELL RENEWAL; CELL SURVIVAL; CHROMOSOMAL INSTABILITY; DEPLETION; DNA REPLICATION; DNA SEQUENCE; DOWN REGULATION; DOWN SYNDROME; EMBRYONIC STEM CELL; ERYTHROCYTE LIFESPAN; GENE DELETION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNOPHENOTYPING; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; PATHOGENESIS; PREMATURE AGING; PRIORITY JOURNAL; PROGEROID SYNDROME; SENESCENCE; STEM CELL; T CELL DEPLETION; TUMOR SUPPRESSOR GENE; UPREGULATION;

ADULT STEM CELLS; ANIMALS; CELL AGING; CELL COUNT; CELL DIFFERENTIATION; CELL DIVISION; DNA REPAIR-DEFICIENCY DISORDERS; HUMANS; MODELS, ANIMAL; STEM CELLS; SYNDROME;

EID: 36349037051     PISSN: 14623994     EISSN: 14623994     Source Type: Journal    
DOI: 10.1017/S146239940700049X     Document Type: Article

References (153)

1. Thomson, J.A. et al. (1998) Embryonic stem cell lines derived from human blastocysts. Science 282, 1145-1147
2. Reubinoff, B.E. et al. (2000) Embryonic stem cell lines from human blastocysts: Somatic differentiation in vitro. Nat Biotechnol 18, 399-404
3. Weissman, I.L. (2000) Stem cells: Units of development, units of regeneration, and units in evolution. Cell 100, 157-168
4. Watt, F.M. (2000) Epidermal stem cells as targets for gene transfer. Hum Gene Ther 11, 2261-2266
5. Whitehead, R.H. et al. (1999) Clonogenic growth of epithelial cells from normal colonic mucosa from both mice and humans. Gastroenterology 117, 858-865
6. Potten, C.S. et al. (2003) Identification of a putative intestinal stem cell and early lineage marker; musashi-1. Differentiation 71, 28-41
7. Wagers, A.J. and Conboy, I.M. (2005) Cellular and molecular signatures of muscle regeneration: Current concepts and controversies in adult myogenesis. Cell 122, 659-667
8. Gage, F.H. (2000) Mammalian neural stem cells. Science 287, 1433-1438
9. Alison, M. (2002) Hepatic stem cells. Transplant Proc 34, 2702-2705
10. Clarke, R.B. (2005) Isolation and characterization of human mammary stem cells. Cell Proliferation 38, 375-386
11. Lechner, A. and Habener, J.F. (2003) Stem/progenitor cells derived from adult tissues: Potential for the treatment of diabetes mellitus. Am J Physiol Endocrinol Metab 284, E259-266
12. Siminovitch, L., Till, J.E. and McCulloch, E.A. (1964) Decline In Colony-Forming Ability Of Marrow Cells Subjected To Serial Transplantation Into Irradiated Mice. J Cell Physiol 64, 23-31
13. Rando, T.A. (2007) The immortal strand hypothesis: Segregation and reconstruction. Cell 129, 1239-1243
14. Lansdorp, P.M. (2007) Immortal strands? Give me a break. Cell 129, 1244-1247
15. Wright, L.S. et al. (2003) Gene expression in human neural stem cells: effects of leukemia inhibitory factor. J Neurochem 86, 179-195
16. Rossi, D.J. et al. (2005) Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc Natl Acad Sci U S A 102, 9194-9199
17. Rossi, D.J. et al. (2007) Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725
18. Campisi, J. (2001) Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol 11, S27-31
19. Sharpless, N.E. and DePinho, R.A. (2004) Telomeres, stem cells, senescence, and cancer. J Clin Invest 113, 160-168
20. Pelicci, P.G. (2004) Do tumor-suppressive mechanisms contribute to organism aging by inducing stem cell senescence? J Clin Invest 113, 4-7
21. Gil, J. and Peters, G. (2006) Regulation of the INK4b-ARF-INK4a tumour suppressor locus: All for one or one for all. Nat Rev Mol Cell Biol 7, 667-677
22. Dimri, G.P. et al. (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92, 9363-9367
23. Paradis, V. et al. (2001) Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas. Hum Pathol 32, 327-332
24. Lechel, A. et al. (2005) The cellular level of telomere dysfunction determines induction of senescence or apoptosis in vivo. EMBO Rep 6, 275-281
25. Wiemann, S.U. et al. (2002) Hepatocyte telomere shortening and senescence are general markers of human liver cirrhosis. Faseb J 16, 935-942
26. Satyanarayana, A. et al. (2003) Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells. Embo J 22, 4003-4013
27. Sharpless, N.E. and DePinho, R.A. (2004) Telomeres, stem cells, senescence, and cancer. J Clin Invest 113, 160-168
28. Kim, W.Y. and Sharpless, N.E. (2006) The regulation of INK4/ARF in cancer and aging. Cell 127, 265-275
29. Serrano, M. et al. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of 53 and p16INK4a. Cell 88, 593-602
30. Maehama, T. and Dixon, J.E. (1998) The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. J Biol Chem 273, 13375-13378
31. Di Cristofano, A. and Pandolfi, P.P. (2000) The multiple roles of PTEN in tumor suppression. Cell 100, 387-390
32. Hayflick, L. and Moorhead, P.S. (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25, 585-621
33. Blackburn, E.H. (2005) Telomeres and telomerase: Their mechanisms of action and the effects of altering their functions. FEBS Lett 579, 859-862
34. Harley, C.B., Futcher, A.B. and Greider, C.W. (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460
35. de Lange, T. (2002) Protection of mammalian telomeres. Oncogene 21, 532-540
36. Geserick, C. and Blasco, M.A. (2006) Novel roles for telomerase in aging. Mech Ageing Dev 127, 579-583
37. Sherr, C.J. and DePinho, R.A. (2000) Cellular senescence: Mitotic clock or culture shock? Cell 102, 407-410
38. Drayton, S. and Peters, G. (2002) Immortalisation and transformation revisited. Curr Opin Genet Dev 12, 98-104
39. Chin, L. et al. (1999) 53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527-538
40. Molofsky, A.V. et al. (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425, 962-967
41. Iwama, A. et al. (2004) Enhanced self-renewal of hematopoietic stem cells mediated by the polycomb gene product Bmi-1. Immunity 21, 843-851
42. Park, I.K. et al. (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302-305
43. Jacobs, J.J. et al. (1999) The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the ink4a locus. Nature 397, 164-168
44. Itahana, K. et al. (2003) Control of the replicative life span of human fibroblasts by 16 and the polycomb protein Bmi-1. Mol Cell Biol 23, 389-401
45. Guney, I., Wu, S. and Sedivy, J.M. (2006) Reduced c-Myc signaling triggers telomere-independent senescence by regulating Bmi-1 and 16(INK4a). Proc Natl Acad Sci U S A 103, 3645-3650
46. Bruggeman, S.W. et al. (2005) Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. Genes Dev 19, 1438-1443
47. Cantley, L.C. and Neel, B.G. (1999) New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A 96, 4240-4245
48. Stiles, B. et al. (2004) PTENless means more. Dev Biol 273, 175-184
49. Kondo, M. et al. (2003) Biology of hematopoietic stem cells and progenitors: Implications for clinical application. Annu Rev Immunol 21, 759-806
50. Civin, C.I. et al. (1990) Positive stem cell selection-basic science. Prog Clin Biol Res 333, 387-401; discussion 402
51. Brugger, W. et al. (1994) Positively selected autologous blood CD34+ cells and unseparated peripheral blood progenitor cells mediate identical hematopoietic engraftment after high-dose VP16, ifosfamide, carboplatin, and epirubicin. Blood 84, 1421-1426
52. Bhatia, M. et al. (1997) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A 94, 5320-5325
53. Glimm, H. et al. (2001) Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-beta2 microglobulin-null mice. J Clin Invest 107, 199-206
54. Lajtha, L.G. (1979) Stem cell concepts. Differentiation 14, 23-34
55. Barrandon, Y. and Green, H. (1987) Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci U S A 84, 2302-2306
56. Morrison, S.J. et al. (1997) Identification of a lineage of multipotent hematopoietic progenitors. Development 124, 1929-1939
57. Lavker, R.M. et al. (1993) Hair follicle stem cells: Their location, role in hair cycle, and involvement in skin tumor formation. J Invest Dermatol 101, 16S-26S
58. Tumbar, T. et al. (2004) Defining the epithelial stem cell niche in skin. Science 303, 359-363
59. Tamaki, S. et al. (2002) Engraftment of sorted/expanded human central nervous system stem cells from fetal brain. J Neurosci Res 69, 976-986
60. Quirici, N. et al. (2002) Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol 30, 783-791
61. Bensidhoum, M. et al. (2004) Homing of in vitro expanded Stro-1- or Stro-1+ human mesenchymal stem cells into the NOD/SCID mouse and their role in supporting human CD34 cell engraftment. Blood 103, 3313-3319
62. Dennis, J.E. et al. (2002) The STRO-1+ marrow cell population is multipotential. Cells Tissues Organs 170, 73-82
63. Szilvassy, S.J. et al. (1990) Quantitative assay for totipotent reconstituting hematopoietic stem cells by a competitive repopulation strategy. Proc Natl Acad Sci U S A 87, 8736-8740
64. McNiece, I.K. et al. (1990) Colony-forming cells with high proliferative potential (HPP-CFC). Int J Cell Cloning 8, 146-160
65. Bhatia, M. et al. (1998) A newly discovered class of human hematopoietic cells with SCID-repopulating activity. Nat Med 4, 1038-1045
66. Larochelle, A. et al. (1996) Identification of primitive human hematopoietic cells capable of repopulating NOD/SCID mouse bone marrow: implications for gene therapy. Nat Med 2, 1329-1337
67. Bonnet, D. (2002) Haematopoietic stem cells. J Pathol 197, 430-440
68. Larochelle, A. et al. (1995) Engraftment of immune-deficient mice with primitive hematopoietic cells from beta-thalassemia and sickle cell anemia patients: Implications for evaluating human gene therapy protocols. Hum Mol Genet 4, 163-172
69. Cashman, J. et al. (1997) Sustained proliferation, multi-lineage differentiation and maintenance of primitive human haemopoietic cells in NOD/SCID mice transplanted with human cord blood. Br J Haematol 98, 1026-1036
70. Horn, P.A. et al. (2003) Distinct hematopoietic stem/progenitor cell populations are responsible for repopulating NOD/SCID mice compared with nonhuman primates. Blood 102, 4329-4335
71. Schmidt, M. et al. (2002) Polyclonal long-term repopulating stem cell clones in a primate model. Blood 100, 2737-2743
72. Blanpain, C. et al. (2004) Self-renewal, multipotency, and the existence of two cell populations within an epithelial stem cell niche. Cell 118, 635-648
73. Claudinot, S. et al. (2005) Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc Natl Acad Sci U S A 102, 14677-14682
74. Collins, C.A. et al. (2005) Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell 122, 289-301
75. Collins, C.A. et al. (2007) A population of myogenic stem cells that survives skeletal muscle aging. Stem Cells 25, 885-894
76. Ostenfeld, T. et al. (2000) Human neural precursor cells express low levels of telomerase in vitro and show diminishing cell proliferation with extensive axonal outgrowth following transplantation. Exp Neurol 164, 215-226
77. Wright, W.E. and Shay, J.W. (2001) Cellular senescence as a tumor-protection mechanism: The essential role of counting. Curr Opin Genet Dev 11, 98-103
78. Wright, W.E. and Shay, J.W. (2002) Historical claims and current interpretations of replicative aging. Nat Biotechnol 20, 682-688
79. Smogorzewska, A. and de Lange, T. (2002) Different telomere damage signaling pathways in human and mouse cells. Embo J 21, 4338-4348
80. Prowse, K.R. and Greider, C.W. (1995) Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci U S A 92, 4818-4822
81. Blasco, M.A. et al. (1997) Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 91, 25-34
82. Abkowitz, J.L. et al. (2002) Evidence that the number of hematopoietic stem cells per animal is conserved in mammals. Blood 100, 2665-2667
83. Parrinello, S. et al. (2003) Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol 5, 741-747
84. Itahana, K., Campisi, J. and Dimri, G.P. (2004) Mechanisms of cellular senescence in human and mouse cells. Biogerontology 5, 1-10
85. Samper, E. et al. (2002) Long-term repopulating ability of telomerase-deficient murine hematopoietic stem cells. Blood 99, 2767-2775
86. Rudolph, K.L. et al. (1999) Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701-712
87. Lee, H.W. et al. (1998) Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569-574
88. Barlow, C. et al. (1996) Atm-deficient mice: A paradigm of ataxia telangiectasia. Cell 86, 159-171
89. Xu, Y. et al. (1996) Targeted disruption of ATM leads to growth retardation, chromosomal fragmentation during meiosis, immune defects, and thymic lymphoma. Genes Dev 10, 2411-2422
90. Wong, K.K. et al. (2003) Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing. Nature 421, 643-648
91. Epstein, C.J. (1995) Down syndrome (Trisomy 21) (Scriver, C.A. et al., series eds), pp. 749-794, McGraw-Hill, New York
92. Nespoli, L. et al. (1993) Immunological features of Down's syndrome: A review. J Intellect Disabil Res 37, 543-551
93. Rumble, B. et al. (1989) Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N Engl J Med 320, 1446-1452
94. Angelopoulou, N. et al. (2000) Bone mineral density and muscle strength in young men with mental retardation (with and without Down syndrome). Calcif Tissue Int 66, 176-180
95. Creutzig, U. et al. (1996) Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia 10, 1677-1686
96. Vaziri, H. et al. (1993) Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am J Hum Genet 52, 661-667
97. Holmes, D.K. et al. (2006) Hematopoietic progenitor cell deficiency in fetuses and children affected by Down's syndrome. Exp Hematol 34, 1611-1615
98. Flores, I., Cayuela, M.L. and Blasco, M.A. (2005) Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309, 1253-1256
99. Ferron, S. et al. (2004) Telomere shortening and chromosomal instability abrogates proliferation of adult but not embryonic neural stem cells. Development 131, 4059-4070
100. Prasher, J.M. et al. (2005) Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1-/- mice. Embo J 24, 861-871
101. Ito, K. et al. (2006) Reactive oxygen species act through p38 MAPK to limit the lifespan of hematopoietic stem cells. Nat Med 12, 446-451
102. Stepanova, L. and Sorrentino, B.P. (2005) A limited role for p16Ink4a and p19Arf in the loss of hematopoietic stem cells during proliferative stress. Blood 106, 827-832
103. Janzen, V. et al. (2006) Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 443, 421-426
104. Molofsky, A.V. et al. (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443, 448-452
105. Yuan, Y. et al. (2004) In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C. Nat Cell Biol 6, 436-442
106. Yu, H. et al. (2006) Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners. Blood 107, 1200-1206
107. Choudhury, A.R. et al. (2007) Cdkn1a deletion improves stem cell function and lifespan of mice with dysfunctional telomeres without accelerating cancer formation. Nat Genet 39, 99-105
108. Cheng, T. et al. (2000) Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287, 1804-1808
109. Kippin, T.E. et al. (2004) Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain. J Neurosci 24, 2832-2836
110. Dumble, M. et al. (2007) The impact of altered p53 dosage on hematopoietic stem cell dynamics during aging. Blood 109, 1736-1742
111. Walkley, C.R. et al. (2005) Negative cell-cycle regulators cooperatively control self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol 7, 172-178
112. Cheng, T. et al. (2000) Stem cell repopulation efficiency but not pool size is governed by p27(kip1). Nat Med 6, 1235-1240
113. Zhang, J. et al. (2006) PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441, 518-522
114. Lessard, J. and Sauvageau, G. (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423, 255-260
115. Molofsky, A.V. et al. (2005) Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev 19, 1432-1437
116. Brun, A.C. et al. (2004) Hoxb4-deficient mice undergo normal hematopoietic development but exhibit a mild proliferation defect in hematopoietic stem cells. Blood 103, 4126-4133
117. Bjornsson, J.M. et al. (2003) Reduced proliferative capacity of hematopoietic stem cells deficient in Hoxb3 and Hoxb4. Mol Cell Biol 23, 3872-3883
118. Miyake, N. et al. (2006) HOXB4-induced self-renewal of hematopoietic stem cells is significantly enhanced by p21 deficiency. Stem Cells 24, 653-661
119. Walkley, C.R. and Orkin, S.H. (2006) Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells. Proc Natl Acad Sci U S A 103, 9057-9062
120. Chien, W.M. et al. (2006) Genetic mosaics reveal both cell-autonomous and cell-nonautonomous function of murine p27Kip1. Proc Natl Acad Sci U S A 103, 4122-4127
121. Sudo, K. et al. (2000) Age-associated characteristics of murine hematopoietic stem cells. J Exp Med 192, 1273-1280
122. Pearce, D.J. et al. (2006) Age-dependent increase in side population distribution within hematopoiesis: Implications for our understanding of the mechanism of aging. Stem Cells 5, 828-835
123. Morrison, S.J. et al. (1996) The aging of hematopoietic stem cells. Nat Med 2, 1011-1016
124. Gibson, M.C. and Schultz, E. (1983) Age-related differences in absolute numbers of skeletal muscle satellite cells. Muscle Nerve 6, 574-580
125. Conboy, I.M. et al. (2003) Notch-mediated restoration of regenerative potential to aged muscle. Science 302, 1575-1577
126. Brack, A.S., Bildsoe, H. and Hughes, S.M. (2005) Evidence that satellite cell decrement contributes to preferential decline in nuclear number from large fibres during murine age-related muscle atrophy. J Cell Sci 118, 4813-4821
127. Ogden, D.A. and Mickliem, H.S. (1976) The fate of serially transplanted bone marrow cell populations from young and old donors. Transplantation 22, 287-293
128. Liang, Y., Van Zant, G. and Szilvassy, S.J. (2005) Effects of aging on the homing and engraftment of murine hematopoietic stem and progenitor cells. Blood 106, 1479-1487
129. Baxter, M.A. et al. (2004) Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22, 675-682
130. Lipschitz, D.A., Mitchell, C.O. and Thompson, C. (1981) The anemia of senescence. Am J Hematol 11, 47-54
131. Harstock, R.J., Smith, E.B. and Ketter, C.S. (1965) Normal variation with aging of the amount of hematopoietic tissue in bone marrow from anterior iliac crest. Am J Clin Pathol 43, 325-333
132. Bagnara, G.P. et al. (2000) Hemopoiesis in healthy old people and centenarians: Well-maintained responsiveness of CD34+ cells to hemopoietic growth factors and remodeling of cytokine network. J Gerontol A Biol Sci Med Sci 55, B61-66; discussion B67-70
133. Ho, A.D., Wagner, W. and Mahlknecht, U. (2005) Stem cells and ageing. The potential of stem cells to overcome age-related deteriorations of the body in regenerative medicine. EMBO Rep 6 Spec No, S35-38
134. Gale, R.E. et al. (1997) Acquired skewing of X-chromosome inactivation patterns in myeloid cells of the elderly suggests stochastic clonal loss with age. Br J Haematol 98, 512-519
135. Morrison, S.J. et al. (1996) Telomerase activity in hematopoietic cells is associated with self-renewal potential. Immunity 5, 207-216
136. Lansdorp, P.M. (1995) Telomere length and proliferation potential of hematopoietic stem cells. J Cell Sci 108, 1-6
137. Rufer, N. et al. (1998) Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol 16, 743-747
138. Vaziri, H. et al. (1994) Evidence for a mitotic clock in human hematopoietic stem cells: Loss of telomeric DNA with age. Proc Natl Acad Sci U S A 91, 9857-9860
139. Wynn, R. et al. (1999) Telomere shortening in leucocyte subsets of long-term survivors of allogeneic bone marrow transplantation. Br J Haematol 105, 997-1001
140. Notaro, R. et al. (1997) In vivo telomere dynamics of human hematopoietic stem cells. Proc Natl Acad Sci U S A 94, 13782-13785
141. Allsopp, R.C. et al. (2003) Telomerase is required to slow telomere shortening and extend replicative lifespan of HSCs during serial transplantation. Blood 102, 517-520
142. Mason, P.J., Wilson, D.B. and Bessler, M. (2005) Dyskeratosis congenita - a disease of dysfunctional telomere maintenance. Curr Mol Med 5, 159-170
143. Cawthon, R.M. et al. (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361, 393-395
144. Kruger, G.M. and Morrison, S.J. (2002) Brain repair by endogenous progenitors. Cell 110, 399-402
145. De Felice, L. et al. (2005) Histone deacetylase inhibitor valproic acid enhances the cytokine-induced expansion of human hematopoietic stem cells. Cancer Res 65, 1505-1513
146. Bug, G. et al. (2005) Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells. Cancer Res 65, 2537-2541
147. Chen, S. et al. (2006) Self-renewal of embryonic stem cells by a small molecule. Proc Natl Acad Sci U S A 103, 17266-17271
148. Trowbridge, J.J. et al. (2006) Glycogen synthase kinase-3 is an in vivo regulator of hematopoietic stem cell repopulation. Nat Med 12, 89-98
149. Sato, N. et al. (2004) Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor. Nat Med 10, 55-63
150. Halaschek-Wiener, J. and Brooks-Wilson, A. (2007) Progeria of stem cells: Stem cell exhaustion in Hutchinson-Gilford progeria syndrome. J Gerontol A Biol Sci Med Sci 62, 3-8
151. Ramirez, C.L et al. (2007) Human progeroid syndromes, aging and cancer: new genetic and epigenetic insights into old questions. Cell Mol Life Sci 64, 155-170
152. Kudlow, B.A., Kennedy, B.K. and Monnat, R.J., Jr. (2007) Werner and Hutchinson-Gilford progeria syndromes: Mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol 8, 394-404
153. Conboy, I.M. et al. (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760-764