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    Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity

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    Authors
    Kim, Sangkyu
    Bi, Xiuhua
    Czarny-Ratajczak, Malwina
    Dai, Jianliang
    Welsh, David A.
    Myers, Leann
    Welsch, Michael A.
    Cherry, Katie E
    Arnold, Jonathan
    Poon, Leonard W.
    Jazwinski, S. Michal
    Show allShow less
    Affiliation
    Tulane University Health Sciences Center
    Issue Date
    2012-04
    Subjects
    telomeres
    age
    ageing
    
    Metadata
    Show full item record
    Abstract
    Leukocyte telomere length is widely considered a biomarker of human age and in many studies indicative of health or disease. We have obtained quantitative estimates of telomere length from blood leukocytes in a population sample, confirming results of previous studies that telomere length significantly decreases with age. Telomere length was also positively associated with several measures of healthy aging, but this relationship was dependent on age. We screened two genes known to be involved in telomere maintenance for association with the age-related decline in telomere length observed in our population to identify candidate longevity-associated genes. A single-nucleotide polymorphism located in the SIRT1 gene and another in the 3' flanking region of XRCC6 had significant effects on telomere length. At each bi-allelic locus, the minor variant was associated with longer telomeres, though the mode of inheritance fitting best differed between the two genes. No statistical interaction was detected for telomere length between the SIRT1 and XRCC6 variants or between these polymorphisms and age. The SIRT1 locus was significantly associated with longevity (P < 0.003). The frequency of the minor allele was higher in long-lived cases than in young controls, which coincides with the protective role of the minor variant for telomere length. In contrast, the XRCC6 variant was not associated with longevity. Furthermore, it did not affect the association of SIRT1 with exceptional survival. The association of the same variant of SIRT1 with longevity was near significant (P < 0.07) in a second population. These results suggest a potential role of SIRT1 in linking telomere length and longevity. Given the differences between this gene and XRCC6, they point to the distinct impact that alternate pathways of telomere maintenance may have on aging and exceptional survival.
    Citation
    Kim, S. et al (2012) 'Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity'. Biogerontology 13 (2):119-31
    Publisher
    Springer
    Journal
    Biogerontology
    URI
    http://hdl.handle.net/10547/594764
    DOI
    10.1007/s10522-011-9360-5
    PubMed ID
    21972126
    PubMed Central ID
    PMC3272146
    Additional Links
    http://link.springer.com/article/10.1007/s10522-011-9360-5
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3272146/
    Type
    Article
    Language
    en
    ISSN
    1573-6768
    ae974a485f413a2113503eed53cd6c53
    10.1007/s10522-011-9360-5
    Scopus Count
    Collections
    Muscle Cellular and Molecular Physiology

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