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Initiation of Genomic Instability, Cellular Senescence, and Organismal Aging by Dysfunctional Telomeres

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Telomeres and Telomerase in Ageing, Disease, and Cancer

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Telomeres are ribonucleoprotein structures that protect the end of linear chromosomes from recognition as DNA double-stranded breaks and activation of a DNA damage response. Telomere-associated proteins also regulate telomerase, the protein responsible for maintaining telomere length. Loss of telomere function results from either alteration in the telosome/shelterin complex that exerts capping function at telomeres, or from progressive loss of telomeric repeats necessary to maintain proper telomeric structure. Dysfunctional telomeres activate p53 to initiate cell cycle arrest/ cellular senescence and may play an important role in aging. Here I describe the use of mouse models to probe the impact of dysfunctional telomeres upon organismal aging.

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  1. Department of Cancer Genetics and Hematopathology, The M.D. Anderson Cancer Center, Houston, TX, USA

    Sandy Chang

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  1. University of Ulm, Albert-Einstein-Allee 11, 89091, Ulm, Germany

    K. Lenhard Rudolph

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Chang, S. (2008). Initiation of Genomic Instability, Cellular Senescence, and Organismal Aging by Dysfunctional Telomeres. In: Rudolph, K.L. (eds) Telomeres and Telomerase in Ageing, Disease, and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-73709-4_4

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