Document Detail

Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity.
MedLine Citation:
PMID:  21972126     Owner:  NLM     Status:  MEDLINE    
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.
Sangkyu Kim; Xiuhua Bi; Malwina Czarny-Ratajczak; Jianliang Dai; David A Welsh; Leann Myers; Michael A Welsch; Katie E Cherry; Jonathan Arnold; Leonard W Poon; S Michal Jazwinski
Related Documents :
9819336 - Copulation rate and sperm use by female bearded tits, panurus biarmicus.
16436666 - Failure of elastic fiber homeostasis leads to pelvic floor disorders.
15831636 - Atherosclerosis-like lesions of the aortic valve are common in adults of all ages: a ne...
22352436 - Epigenetic-mediated decline in synaptic plasticity during aging.
19497556 - Ergonomic risk factors for the wrists of hairdressers.
15149406 - Variable selection in platanthera bifolia (orchidaceae): phenotypic selection differed ...
Publication Detail:
Type:  Journal Article; Multicenter Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-05
Journal Detail:
Title:  Biogerontology     Volume:  13     ISSN:  1573-6768     ISO Abbreviation:  Biogerontology     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-10     Completed Date:  2012-08-06     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  100930043     Medline TA:  Biogerontology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  119-31     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
3' Flanking Region
Age Factors
Aged, 80 and over
Antigens, Nuclear / genetics*,  metabolism
Case-Control Studies
DNA-Binding Proteins / genetics*,  metabolism
Gene Frequency
Lod Score
Longevity / genetics*
Middle Aged
Multivariate Analysis
Odds Ratio
Polymorphism, Single Nucleotide*
Proportional Hazards Models
Sirtuin 1 / genetics*,  metabolism
Survival Analysis
Telomere / metabolism*
Telomere Shortening*
Young Adult
Grant Support
P01 AG017553-05/AG/NIA NIH HHS; P01 AG022064/AG/NIA NIH HHS; P01 AG022064-06/AG/NIA NIH HHS; P01AG017553/AG/NIA NIH HHS; P01AG022064/AG/NIA NIH HHS
Reg. No./Substance:
0/Antigens, Nuclear; 0/DNA-Binding Proteins; 0/Ku autoantigen; EC 3.5.1.-/SIRT1 protein, human; EC 3.5.1.-/Sirtuin 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Association of body mass index with symptom severity and quality of life in patients with fibromyalg...
Next Document:  Solution-Based Synthesis and Design of Late Transition Metal Chalcogenide Materials for Oxygen Reduc...