SIRT6 in DNA repair, metabolism and ageing

Authors

  • D. B. Lombard,

    1. From the Howard Hughes Medical Institute, The Children’s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School
    2. Department of Pathology, Brigham and Women’s Hospital, Boston, MA, USA
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  • B. Schwer,

    1. From the Howard Hughes Medical Institute, The Children’s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School
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  • F. W. Alt,

    1. From the Howard Hughes Medical Institute, The Children’s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School
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  • R. Mostoslavsky

    1. From the Howard Hughes Medical Institute, The Children’s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School
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    • *

      Present address: Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA


Abstract.

Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1-like signalling. In addition, homologs of yeast Sir2 – the sirtuins – regulate lifespan in diverse organisms. Here, we focus on one particular sirtuin, SIRT6. Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan.

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