Authors: Kim S; Bi X; Czarny-Ratajczak M; Dai J; Welsh DA; Myers L; Welsch MA; Cherry KE; Arnold J; Poon LW; Jazwinski SM
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.
Keywords: 3' Flanking Region; Adult; Age Factors; Aged; Aged, 80 and over; Antigens, Nuclear/*genetics/metabolism; Case-Control Studies; DNA-Binding Proteins/*genetics/metabolism; Female; Gene Frequency; Genotype; Georgia; Humans; Lod Score; Longevity/*genetics; Louisiana; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Phenotype; *Polymorphism, Single Nucleotide; Proportional Hazards Models; Sirtuin 1/*genetics/metabolism; Survival Analysis; Telomere/*metabolism; *Telomere Shortening; Young Adult|
Journal: Biogerontology Volume: 13 Issue: 2 Pages: 119-31 Date: Oct. 6, 2011 PMID: 21972126 |
224 nonagenarian cases (84 male, 140 female, 90- 103 y) and 293 young controls (100 male, 193 female, 21- 59 y) from the Louisiana Healthy Aging Study were examined for longevity association study. Then, 170 subjects (25 male, 145 female, ≥98 y) and 220 young controls (84 male, 136 female, 20–59 y) from the Georgia Centenarian Study were examined to replicate the results.
rs132793 in XRCC6 had significant effect on telomere length, but it was not associated with longevity.
Kim S, Bi X, Czarny-Ratajczak M, Dai J, Welsh DA, Myers L, Welsch MA, Cherry KE, Arnold J, Poon LW, Jazwinski SM (2012) Telomere maintenance genes SIRT1 and XRCC6 impact age-related decline in telomere length but only SIRT1 is associated with human longevity. Biogerontology 13: 119-31.
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