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

Content Provider	Springer Nature Link
Author	Kim, Sangkyu Bi, Xiuhua Czarny Ratajczak, Malwina Dai, Jianliang Welsh, David A. Myers, Leann Welsch, Michael A. Cherry, Katie E. Arld, Jonathan Poon, Leonard W. Jazwinski, S. Michal
Copyright Year	2011
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.
Starting Page	119
Ending Page	131
Page Count	13
File Format	PDF
ISSN	13895729
Journal	Biogerontology
Volume Number	13
Issue Number	2
e-ISSN	15736768
Language	English
Publisher	Springer Netherlands
Publisher Date	2011-10-05
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	SIRT1 XRCC6 Ku Telomeres Aging Longevity Developmental Biology Cell Biology Geriatrics/Gerontology
Content Type	Text
Resource Type	Article
Subject	Aging Gerontology Geriatrics and Gerontology

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