Telomere length, stem cells and aging

Abstract

Telomere shortening occurs concomitant with organismal aging, and it is accelerated in the context of human diseases associated with mutations in telomerase, such as some cases of dyskeratosis congenita, idiopathic pulmonary fibrosis and aplastic anemia. People with these diseases, as well as Terc-deficient mice, show decreased lifespan coincidental with a premature loss of tissue renewal, which suggests that telomerase is rate-limiting for tissue homeostasis and organismal survival. These findings have gained special relevance as they suggest that telomerase activity and telomere length can directly affect the ability of stem cells to regenerate tissues. If this is true, stem cell dysfunction provoked by telomere shortening may be one of the mechanisms responsible for organismal aging in both humans and mice. Here, we will review the current evidence linking telomere shortening to aging and stem cell dysfunction.

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Figure 1: Telomere structure.
Figure 2: Telomere elongation mechanisms.
Figure 3: The telomerase knockout mouse as a model for telomere-induced aging.
Figure 4: A stem cell theory for the role of telomeres and telomerase in cancer and aging.
Figure 5: Antagonistic effects of telomerase in cancer and aging.

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Acknowledgements

M.A. Blasco's laboratory is funded by the MCyT (SAF2005-00277, GEN2001 4856-C13-08), the Regional Government of Madrid (GR/SAL/0597/2004), the European Union (TELOSENS FIGH-CT-2002-00217, INTACT LSHC-CT-2003 506803, ZINCAGE FOOD-CT-2003-506850, RISC-RAD FI6R-CT-2003-508842, MOL CANCER MED LSHC-CT-2004-502943) and the Josef Steiner Cancer Research Award 2003.

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Correspondence to Maria A Blasco.

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Blasco, M. Telomere length, stem cells and aging. Nat Chem Biol 3, 640–649 (2007). https://doi.org/10.1038/nchembio.2007.38

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