Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Emerging models and paradigms for stem cell ageing

Abstract

Ageing is accompanied by a progressive decline in stem cell function, resulting in less effective tissue homeostasis and repair. Here we discuss emerging invertebrate models that provide insights into molecular pathways of age-related stem cell dysfunction in mammals, and we present various paradigms of how stem cell functionality changes with age, including impaired self-renewal and aberrant differentiation potential.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Emerging paradigms for stem cell ageing.

References

  1. Kirkwood, T. B. Understanding the odd science of aging. Cell 120, 437–447 (2005).

    CAS  Article  PubMed  Google Scholar 

  2. Gopinath, S. D. & Rando, T. A. Stem cell review series: aging of the skeletal muscle stem cell niche. Aging Cell 7, 590–598 (2008).

    CAS  PubMed  Google Scholar 

  3. Drummond-Barbosa, D. Stem cells, their niches and the systemic environment: an aging network. Genetics 180, 1787–1797 (2008).

    PubMed  PubMed Central  Google Scholar 

  4. Ferraro, F., Celso, C. L. & Scadden, D. Adult stem cells and their niches. Adv. Exp. Med. Biol. 695, 155–168 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Rando, T. A. Stem cells, ageing and the quest for immortality. Nature 441, 1080–1086 (2006).

    CAS  PubMed  Google Scholar 

  6. Sharpless, N. E. & DePinho, R. A. How stem cells age and why this makes us grow old. Nat Rev. Mol Cell Biol 8, 703–713 (2007).

    CAS  PubMed  Google Scholar 

  7. Pollina, E. A. & Brunet, A. Epigenetic regulation of aging stem cells. Oncogene 10.1038/onc.2011.45 (in the press).

  8. Liu, L. & Rando T. A. Manifestations and mechanisms of stem cell aging. J. Cell Biol. 193, 257–266 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Kennedy, B. K. The genetics of ageing: insight from genome-wide approaches in invertebrate model organisms. J. Intern. Med. 263, 142–152 (2008).

    CAS  PubMed  Google Scholar 

  10. Kenyon, C. J. The genetics of ageing. Nature 464, 504–512 (2010).

    CAS  PubMed  Google Scholar 

  11. Friedman, D. B. & Johnson, T. E. A mutation in the age-1 gene in Caenorhabditis elegans lengthens life and reduces hermaphrodite fertility. Genetics 118, 75–86 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Kenyon, C., Chang, J., Gensch, E., Rudner, A. & Tabtiang, R. A C. elegans mutant that lives twice as long as wild type. Nature 366, 461–464 (1993).

    CAS  PubMed  Google Scholar 

  13. Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277, 942–946 (1997).

    CAS  PubMed  Google Scholar 

  14. Mair, W. & Dillin, A. Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77, 727–754 (2008).

    CAS  PubMed  Google Scholar 

  15. Kapahi, P. et al. With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab. 11, 453–465 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Bjedov, I. et al. Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab. 11, 35–46 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Jasper, H. & Jones, D. L. Metabolic regulation of stem cell behavior and implications for aging. Cell Metab. 12, 561–565 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Rafalski, V. A. & Brunet, A. Energy metabolism in adult neural stem cell fate. Prog. Neurobiol. 93, 182–203 (2011).

    CAS  PubMed  Google Scholar 

  19. Yilmaz, O. H. et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475–482 (2006).

    CAS  PubMed  Google Scholar 

  20. Lee, J. Y. et al. mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion. Cell Stem Cell 7, 593–605 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Steinkraus, K. A., Kaeberlein, M. & Kennedy, B. K. Replicative aging in yeast: the means to the end. Annu. Rev. Cell Dev. Biol. 24, 29–54 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Mortimer, R. & Johnston, J. Life span of individual yeast cells. Nature 183, 1751–1752 (1959).

    CAS  PubMed  Google Scholar 

  23. Kennedy, B. K., Austriaco, N. R. Jr, Zhang, J. & Guarente, L. Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80, 485–496 (1995).

    CAS  PubMed  Google Scholar 

  24. Wood, J. G. et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430, 686–689 (2004).

    CAS  PubMed  Google Scholar 

  25. Fabrizio, P. & Longo, V. D. The chronological life span of Saccharomyces cerevisiae. Aging Cell 2, 73–81 (2003).

    CAS  PubMed  Google Scholar 

  26. Aguilaniu, H., Gustafsson, L., Rigoulet, M. & Nystrom, T. Asymmetric inheritance of oxidatively damaged proteins during cytokinesis. Science 299, 1751–1753 (2003).

    CAS  PubMed  Google Scholar 

  27. Hsin, H. & Kenyon, C. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362–366 (1999).

    CAS  PubMed  Google Scholar 

  28. Arantes-Oliveira, N., Apfeld, J., Dillin, A. & Kenyon, C. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans. Science 295, 502–505 (2002).

    CAS  PubMed  Google Scholar 

  29. Greer, E. L. et al. Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 466, 383–387 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Wang, M. C., O'Rourke, E. J. & Ruvkun, G. Fat metabolism links germline stem cells and longevity in C. elegans. Science 322, 957–960 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Helfand, S. L. & Rogina, B. Molecular genetics of aging in the fly: is this the end of the beginning? Bioessays 25, 134–141 (2003).

    CAS  PubMed  Google Scholar 

  32. Voog, J. & Jones, D. L. Stem cells and the niche: a dynamic duo. Cell Stem Cell 6, 103–115 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Singh, S. R., Liu, W. & Hou, S. X. The adult Drosophila malpighian tubules are maintained by multipotent stem cells. Cell Stem Cell 1, 191–203 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Takashima, S., Mkrtchyan, M., Younossi-Hartenstein, A., Merriam, J. R. & Hartenstein, V. The behaviour of Drosophila adult hindgut stem cells is controlled by Wnt and Hh signalling. Nature 454, 651–655 (2008).

    CAS  PubMed  Google Scholar 

  35. Fox, D. T. & Spradling, A. C. The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage. Cell Stem Cell 5, 290–297 (2009).

    CAS  PubMed  Google Scholar 

  36. Fuller, M. T. & Spradling, A. C. Male and female Drosophila germline stem cells: two versions of immortality. Science 316, 402–404 (2007).

    CAS  PubMed  Google Scholar 

  37. Ohlstein, B. & Spradling, A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439, 470–474 (2006).

    CAS  PubMed  Google Scholar 

  38. Micchelli, C. A. & Perrimon, N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475–479 (2006).

    CAS  PubMed  Google Scholar 

  39. Lin, G., Xu, N. & Xi, R. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455, 1119–1123 (2008).

    CAS  PubMed  Google Scholar 

  40. Renault, V. M. et al. FoxO3 regulates neural stem cell homeostasis. Cell Stem Cell 5, 527–539 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Inomata, K. et al. Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation. Cell 137, 1088–1099 (2009).

    CAS  PubMed  Google Scholar 

  42. Paik, J. H. et al. FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell 5, 540–553 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Wallenfang, M. R., Nayak, R. & DiNardo, S. Dynamics of the male germline stem cell population during aging of Drosophila melanogaster. Aging Cell 5, 297–304 (2006).

    CAS  PubMed  Google Scholar 

  44. Boyle, M., Wong, C., Rocha, M. & Jones, D. L. Decline in self-renewal factors contributes to aging of the stem cell niche in the Drosophila testis. Cell Stem Cell 1, 470–478 (2007).

    CAS  PubMed  Google Scholar 

  45. Pan, L. et al. Stem cell aging is controlled both intrinsically and extrinsically in the Drosophila ovary. Cell Stem Cell 1, 458–469 (2007).

    CAS  PubMed  Google Scholar 

  46. Cheng, J. et al. Centrosome misorientation reduces stem cell division during ageing. Nature 456, 599–604 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Margolis, J. & Spradling, A. Identification and behavior of epithelial stem cells in the Drosophila ovary. Development 121, 3797–3807 (1995).

    CAS  PubMed  Google Scholar 

  48. Xie, T. & Spradling, A. C. A niche maintaining germ line stem cells in the Drosophila ovary. Science 290, 328–330 (2000).

    CAS  PubMed  Google Scholar 

  49. Conboy, I. M., Conboy, M. J., Smythe, G. M. & Rando, T. A. Notch-mediated restoration of regenerative potential to aged muscle. Science 302, 1575–1577 (2003).

    CAS  PubMed  Google Scholar 

  50. Brack, A. S. et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 317, 807–810 (2007).

    CAS  PubMed  Google Scholar 

  51. Conboy, I. M. & Rando, T. A. The regulation of Notch signaling controls satellite cell activation and cell fate determination in postnatal myogenesis. Dev. Cell 3, 397–409 (2002).

    CAS  PubMed  Google Scholar 

  52. Conboy, I. M. et al. Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433, 760–764 (2005).

    CAS  PubMed  Google Scholar 

  53. Carlson, B. M. & Faulkner, J. A. Muscle transplantation between young and old rats: age of host determines recovery. Am. J Physiol. 256, C1262–C1266 (1989).

    CAS  PubMed  Google Scholar 

  54. Conboy, I. M. & Rando, T. A. Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle 4, 407–410 (2005).

    CAS  PubMed  Google Scholar 

  55. LaFever, L. & Drummond-Barbosa, D. Direct control of germline stem cell division and cyst growth by neural insulin in Drosophila. Science 309, 1071–1073 (2005).

    CAS  PubMed  Google Scholar 

  56. Hsu, H. J. & Drummond-Barbosa, D. Insulin levels control female germline stem cell maintenance via the niche in Drosophila. Proc. Natl Acad. Sci. USA 106, 1117–1121 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Ueishi, S., Shimizu, H. & Inoue, H. Male germline stem cell division and spermatocyte growth require insulin signaling in Drosophila. Cell Struct. Funct. 34, 61–69 (2009).

    PubMed  Google Scholar 

  58. Wang, L. & Jones, D. L. The effects of aging on stem cell behavior in Drosophila. Exp. Gerontol. 10.1016/j.exger.2010.10.005 (in the press).

  59. Carlson, M. E. et al. Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell 8, 676–689 (2009).

    CAS  PubMed  Google Scholar 

  60. Rossi, D. J. et al. Cell intrinsic alterations underlie hematopoietic stem cell aging. Proc. Natl Acad. Sci USA. 102, 9194–9199 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Beerman, I. et al. Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc. Natl Acad. Sci. USA 107, 5465–5470 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Cho, R. H., Sieburg, H. B. & Muller-Sieburg, C. E. A new mechanism for the aging of hematopoietic stem cells: aging changes the clonal composition of the stem cell compartment but not individual stem cells. Blood 111, 5553–5561 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Challen, G. A., Boles, N. C., Chambers, S. M. & Goodell, M. A. Distinct hematopoietic stem cell subtypes are differentially regulated by TGF-β1. Cell Stem Cell 6, 265–278 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Choi, Y. J. et al. Age-related upregulation of Drosophila caudal gene via NF-κB in the adult posterior midgut. Biochim. Biophys. Acta 1780, 1093–1100 (2008).

    CAS  PubMed  Google Scholar 

  65. Biteau, B., Hochmuth, C. E. & Jasper, H. JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3, 442–455 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Park, J. S., Kim, Y. S. & Yoo, M. A. The role of p38b MAPK in age-related modulation of intestinal stem cell proliferation and differentiation in Drosophila. Aging 1, 637–651 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Jiang, H. et al. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343–1355 (2009).

    PubMed  PubMed Central  Google Scholar 

  68. Amcheslavsky, A., Jiang, J. & Ip, Y. T. Tissue damage-induced intestinal stem cell division in Drosophila. Cell Stem Cell 4, 49–61 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Buchon, N., Broderick, N. A., Chakrabarti, S. & Lemaitre, B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 23, 2333–2344 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Biteau, B. et al. Lifespan extension by preserving proliferative homeostasis in Drosophila. PLoS. Genet. 6, e1001159 (2010).

    PubMed  PubMed Central  Google Scholar 

  71. Wessells, R. J., Fitzgerald, E., Cypser, J. R., Tatar, M. & Bodmer, R. Insulin regulation of heart function in aging fruit flies. Nat. Genet. 36, 1275–1281 (2004).

    CAS  PubMed  Google Scholar 

  72. Demontis, F. & Perrimon, N. FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143, 813–825 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Lin, G., Xu, N. & Xi, R. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature 455, 1119–1123 (2008).

    CAS  PubMed  Google Scholar 

  74. Campisi, J. Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120, 513–522 (2005).

    CAS  PubMed  Google Scholar 

  75. Kuro-o M. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51 (1997).

    CAS  PubMed  Google Scholar 

  76. Kuro-o M. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr. Opin. Nephrol. Hypertens. 15, 437–441 (2006).

    CAS  PubMed  Google Scholar 

  77. Liu, H. et al. Augmented Wnt signaling in a mammalian model of accelerated aging. Science. 317, 803–806 (2007).

    CAS  PubMed  Google Scholar 

  78. Ayoub, N., Jeyasekharan, A. D., Bernal, J. A. & Venkitaraman, A. R. Paving the way for H2AX phosphorylation: chromatin changes in the DNA damage response. Cell Cycle 8, 1494–1500 (2009).

    CAS  PubMed  Google Scholar 

  79. Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 447, 725–729 (2007).

    CAS  PubMed  Google Scholar 

  80. Charville, G. W. & Rando, T. A. Stem cell ageing and non-random chromosome segregation. Philos. Trans. R. Soc. Lond B Biol. Sci. 366, 85–93 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Chambers, S. M. et al. Aging hematopoietic stem cells decline in function and exhibit epigenetic dysregulation. PLoS Biol. 5, e201 (2007).

    PubMed  PubMed Central  Google Scholar 

  82. Nishino, J., Kim, I., Chada, K. & Morrison, S. J. Hmga2 promotes neural stem cell self-renewal in young but not old mice by reducing p16Ink4a and p19Arf expression. Cell 135, 227–239 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Janzen, V. et al. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature. 443, 421–426 (2006).

    CAS  PubMed  Google Scholar 

  84. Krishnamurthy, J. et al. p16INK4a induces an age-dependent decline in islet regenerative potential. Nature 443, 453–457 (2006).

    CAS  PubMed  Google Scholar 

  85. Signer, R. A., Montecino-Rodriguez, E., Witte, O. N. & Dorshkind, K. Aging and cancer resistance in lymphoid progenitors are linked processes conferred by p16Ink4a and Arf. Genes Dev. 22, 3115–3120 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Liu, Y. et al. Expression of p16(INK4a) in peripheral blood T-cells is a biomarker of human aging. Aging Cell 8, 439–448 (2009).

    CAS  PubMed  Google Scholar 

  87. Blanpain, C., Mohrin, M., Sotiropoulou, P. A. & Passegue, E. DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 8, 16–29 (2011).

    CAS  PubMed  Google Scholar 

  88. Sotiropoulou, P. A. et al. Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat. Cell Biol. 12, 572–582 (2010).

    CAS  PubMed  Google Scholar 

  89. von, F. G., Hartmann, D., Song, Z. & Rudolph, K. L. Role of telomere dysfunction in aging and its detection by biomarkers. J. Mol. Med. 87, 1165–1171 (2009).

    Google Scholar 

  90. Flores, I. & Blasco, M. A. The role of telomeres and telomerase in stem cell aging. FEBS Lett. 584, 3826–3830 (2010).

    CAS  PubMed  Google Scholar 

  91. Ju, Z. et al. Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat. Med. 13, 742–747 (2007).

    CAS  PubMed  Google Scholar 

  92. Song, Z. et al. Alterations of the systemic environment are the primary cause of impaired B and T lymphopoiesis in telomere-dysfunctional mice. Blood 115, 1481–1489 (2010).

    PubMed  Google Scholar 

  93. Janus, F. et al. The dual role model for p53 in maintaining genomic integrity. Cell Mol. Life Sci. 55, 12–27 (1999).

    CAS  PubMed  Google Scholar 

  94. Tyner, S. D. et al. p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45–53 (2002).

    CAS  PubMed  Google Scholar 

  95. Maier, B. et al. Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18, 306–319 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Gannon, H. S., Donehower, L. A., Lyle, S. & Jones, S. N. Mdm2–p53 signaling regulates epidermal stem cell senescence and premature aging phenotypes in mouse skin. Dev. Biol. 353, 1–9 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Matheu, A. et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448, 375–379 (2007).

    CAS  PubMed  Google Scholar 

  98. Medvedev, Z. A. An attempt at a rational classification of theories of ageing. Biol. Rev. Camb. Philos. Soc. 65, 375–398 (1990).

    CAS  PubMed  Google Scholar 

  99. Kirkwood, T. B. & Holliday, R. The evolution of ageing and longevity. Proc. R. Soc. Lond B Biol. Sci. 205, 531–546 (1979).

    CAS  PubMed  Google Scholar 

  100. Medawar, P. B. An Unsolved Problem of Biology (H. K. Lewis, 1952).

    Google Scholar 

  101. Williams, G. C. Pleiotropy, natural selection, and the evolution of senescence. Evolution 11, 398–411 (1957).

    Google Scholar 

  102. Blagosklonny, M. V. Revisiting the antagonistic pleiotropy theory of aging: TOR-driven program and quasi-program. Cell Cycle 9, 3151–3156 (2010).

    CAS  PubMed  Google Scholar 

  103. Harrison, D. E. Proliferative capacity of erythropoietic stem cell lines and aging: an overview. Mech. Ageing Dev. 9, 409–426 (1979).

    CAS  PubMed  Google Scholar 

  104. de, H. G., Nijhof, W. & Van, Z. G. Mouse strain-dependent changes in frequency and proliferation of hematopoietic stem cells during aging: correlation between lifespan and cycling activity. Blood 89, 1543–1550 (1997).

    Google Scholar 

  105. Brack, A. S. & Rando, T. A. Intrinsic changes and extrinsic influences of myogenic stem cell function during aging. Stem Cell Rev. 3, 226–237 (2007).

    CAS  PubMed  Google Scholar 

  106. Ryu, B. Y., Orwig, K. E., Oatley, J. M., Avarbock, M. R. & Brinster, R. L. Effects of aging and niche microenvironment on spermatogonial stem cell self-renewal. Stem Cells 24, 1505–1511 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhang, X., Ebata, K. T., Robaire, B. & Nagano, M. C. Aging of male germ line stem cells in mice. Biol. Reprod. 74, 119–124 (2006).

    CAS  PubMed  Google Scholar 

  108. Kudlow, B. A., Kennedy, B. K. & Monnat, R. J. Jr. Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat. Rev. Mol. Cell Biol. 8, 394–404 (2007).

    CAS  PubMed  Google Scholar 

  109. Sahin, E. & DePinho, R. A. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 464, 520–528 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Burtner, C. R. & Kennedy, B. K. Progeria syndromes and ageing: what is the connection? Nat. Rev. Mol. Cell Biol. 11, 567–578 (2010).

    CAS  PubMed  Google Scholar 

  111. Nijnik, A. et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 447, 686–690 (2007).

    CAS  PubMed  Google Scholar 

  112. Lee, H. W. et al. Essential role of mouse telomerase in highly proliferative organs. Nature 392, 569–574 (1998).

    CAS  PubMed  Google Scholar 

  113. Rudolph, K. L. et al. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell 96, 701–712 (1999).

    CAS  PubMed  Google Scholar 

  114. Jaskelioff, M. et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469, 102–106 (2011).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We apologize to those colleagues whose work could not be referenced directly owing to space constraints. D.L.J. is funded by the Emerald Foundation, the G. Harold and Leila Y. Mathers Charitable Foundation, the ACS, the California Institute for Regenerative Medicine (CIRM), and the NIH (R01 AG028092). T.A.R. is funded by the NIH (R37 AG23806, R01 AR056849 and an NIH Director's Pioneer Award), the Glenn Foundation for Medical Research, the Department of Veterans Affairs (Merit Review) and the Amertical Federation for Aging Research (“Breakthroughs in Gerontology” (BIG) Award).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Thomas A. Rando.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jones, D., Rando, T. Emerging models and paradigms for stem cell ageing. Nat Cell Biol 13, 506–512 (2011). https://doi.org/10.1038/ncb0511-506

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb0511-506

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing